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  • 1. Aaldering, L. J.
    et al.
    Poongavanam, V.
    Langkjær, N.
    Natarajan Arul, Murugan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Jørgensen, P. T.
    Wengel, J.
    Veedu, R. N.
    Development of an Efficient G-Quadruplex-Stabilised Thrombin-Binding Aptamer Containing a Three-Carbon Spacer Molecule2017In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 18, no 8, 755-763 p.Article in journal (Refereed)
    Abstract [en]

    The thrombin-binding aptamer (TBA), which shows anticoagulant properties, is one of the most studied G-quadruplex-forming aptamers. In this study, we investigated the impact of different chemical modifications such as a three-carbon spacer (spacer-C3), unlocked nucleic acid (UNA) and 3′-amino-modified UNA (amino-UNA) on the structural dynamics and stability of TBA. All three modifications were incorporated at three different loop positions (T3, T7, T12) of the TBA G-quadruplex structure to result in a series of TBA variants and their stability was studied by thermal denaturation; folding was studied by circular dichroism spectroscopy and thrombin clotting time. The results showed that spacer-C3 introduction at the T7 loop position (TBA-SP7) significantly improved stability and thrombin clotting time while maintaining a similar binding affinity as TBA to thrombin. Detailed molecular modelling experiments provided novel insights into the experimental observations, further supporting the efficacy of TBA-SP7. The results of this study could provide valuable information for future designs of TBA analogues with superior thrombin inhibition properties. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  • 2. Ashaduzzaman, M.
    et al.
    Anto Antony, A.
    Arul Murugan, Natarajan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Deshpande, S. R.
    Turner, A. P. F.
    Tiwari, A.
    Studies on an on/off-switchable immunosensor for troponin T2015In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 73Article in journal (Refereed)
    Abstract [en]

    Regeneration is a key goal in the design of immunosensors. In this study, we report the temperature-regulated interaction of N-isopropylacrylamide (PNIPAAm) functionalised cardiac troponin T (cTnT) with anti-cTnT. Covalently bonded PNIPAAm on an anti-cTnT bioelectrode showed on/off-switchability, regeneration capacity and temperature triggered sensitivity for cTnT. Above the lower critical solution temperature (LCST), PNIPAAm provides a liphophilic microenvironment with specific volume reduction at the bioelectrode surface, making available binding space for cTnT, and facilitating analyte recognition. Computational studies provide details about the structural changes occurring at the electrode above and below the LCST. Furthermore, free energies associated with the binding of cTnT with PNIPAAm at 25 (δG<inf>coil</inf>=-6.0Kcal/mole) and 37°C (δG<inf>globular</inf>=-41.0kcal/mole) were calculated to elucidate the interaction and stability of the antigen-antibody complex. The responsiveness of such assemblies opens the way for miniaturised, smart immuno-technologies with 'built-in' programmable interactions of antigen-antibody upon receiving stimuli.

  • 3. Ashaduzzaman, Md.
    et al.
    Deshpande, Swapneel R.
    Natarajan Arul, Murugan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Mishra, Yogendra Kumar
    Turner, Anthony P. F.
    Tiwari, Ashutosh
    On/off-switchable LSPR nano-immunoassay for troponin-T2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 44027Article in journal (Refereed)
    Abstract [en]

    Regeneration of immunosensors is a longstanding challenge. We have developed a re-usable troponin-T (TnT) immunoassay based on localised surface plasmon resonance (LSPR) at gold nanorods (GNR). Thermosensitive poly(N-isopropylacrylamide) (PNIPAAM) was functionalised with anti-TnT to control the affinity interaction with TnT. The LSPR was extremely sensitive to the dielectric constant of the surrounding medium as modulated by antigen binding after 20 min incubation at 37 degrees C. Computational modelling incorporating molecular docking, molecular dynamics and free energy calculations was used to elucidate the interactions between the various subsystems namely, IgG-antibody (c. f., anti-TnT), PNIPAAM and/or TnT. This study demonstrates a remarkable temperature dependent immuno-interaction due to changes in the PNIPAAM secondary structures, i.e., globular and coil, at above or below the lower critical solution temperature (LCST). A series of concentrations of TnT were measured by correlating the lambda(LSPR) shift with relative changes in extinction intensity at the distinct plasmonic maximum (i. e., 832 nm). The magnitude of the red shift in lambda(LSPR) was nearly linear with increasing concentration of TnT, over the range 7.6 x 10(-15) to 9.1 x 10(-4) g/mL. The LSPR based nano-immunoassay could be simply regenerated by switching the polymer conformation and creating a gradient of microenvironments between the two states with a modest change in temperature.

  • 4. Awasthi, Saurabh
    et al.
    Murugan, N. Arul
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Saraswathi, N. T.
    Advanced Glycation End Products Modulate Structure and Drug Binding Properties of Albumin2015In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 12, no 9, 3312-3322 p.Article in journal (Refereed)
    Abstract [en]

    The extraordinary ligand binding properties of albumin makes it a key player in the pharmacokinetics and pharmacodynamics of many vital drugs. Albumin is highly susceptible for nonenzymatic glycation mediated structural modifications, and there is a need to determine structural and functional impact of specific AGEs modifications. The present study was aimed toward determining the AGE mediated structure and function changes, primarily looking into the effect on binding affinity of drugs in the two major drug binding sites of albumin. The impact of the two most predominant AGEs modifications, i.e., carboxyethyllysine (CEL) and argpyrimidine (Arg-P), was studied on the basis of the combination of in vitro and in silico experiments. In vitro studies were carried out by AGEs modification of bovine serum albumin (BSA) for the formation of Arg-P and CEL followed by drug interaction studies. In silico studies involved molecular dynamics (MD) simulations and docking studies for native and AGEs modified BSAs. In particular the side chain modification was specifically carried out for the residues in the drug binding sites, i.e., Arg-194, Arg-196, Arg-198, and Arg-217, and Lys-204 (site I) and Arg-409 and Lys-413 (site II). The equilibrated structures of native BSA (n-BSA) and glycated BSA (G-BSA) as obtained from MD were used for drug binding studies using molecular docking approach. It was evident from the results of both in vitro and in silico drug interaction studies that AGEs modification results in the reduced drug binding affinity for tolbutamide (TLB) and ibuprofen (IBP) in sites I and II. Moreover, the AGEs modification mediated conformational changes resulted in the shallow binding pockets with reduced accessibility for drugs.

  • 5.
    Balamurugan, Kanagasabai
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Natarajan Arul, Murugan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Langström, Bengt
    Nordberg, Agneta
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology. Siberian Federal University, Russian Federation.
    Effect of Alzheimer Familial Chromosomal Mutations on the Amyloid Fibril Interaction with Different PET Tracers: Insight from Molecular Modeling Studies2017In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 8, no 12, 2655-2666 p.Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease (AD) is the most common neurodegenerative disorder. Along with an increasing number of elderly worldwide, it poses a great challenge for the society and health care. Although sporadic AD is the common form of AD, 2-3% of the AD cases are expected to be due to mutations in the fi region of the amyloid precursor protein, which is referred to as autosomal dominant AD (ADAD). These mutations may cause changes in the secondary structure of the amyloid fi fibrils and may alter the fibrillization rate leading to changes in the disease development and could also affect the binding to tracers used in diagnosis. In particular, from some recent clinical studies using PET tracers for detection of fibrillar amyloids, it is evident that in ADAD patients with Arctic mutation no amyloid plaque binding can be detected with the "C Pittsburgh Compound B (C-11-PIB). However, for in vitro conditions, significant binding of H-3-PIB has been reported for the amyloid fibrils carrying the Arctic mutation. The aim of the present study is to investigate if there is any mutation specific binding of commonly used amyloid tracers, namely, florbetaben, florbetapir, FPIB, AZD4694, and AZD2184, by means of molecular modeling techniques. Other than Arctic, ADAD mutations, such as the Dutch, Italian, Iowa, and Flemish mutations, are considered in this study. We report that all tracers except florbetapir show reduced binding affinity toward amyloid beta fibrils with the Arctic mutation when compared to the native type. Moreover, florbetapir is the only tracer that binds to all mutants with increased affinity when compared to the native fibril. The results obtained from these studies could increase the understanding of the structural changes caused by mutation and concomitant changes in the interaction pattern of the PET tracers with the mutated variants, which in turn can be useful in selecting the appropriate tracers for the purpose of diagnosis as well as for designing new tracers with desirable properties.

  • 6.
    Balamurugan, Kanagasabai
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Natarajan Arul, Murugan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512). KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Multistep Modeling Strategy To Improve the Binding Affinity Prediction of PET Tracers to A beta(42): Case Study with Styrylbenzoxazole Derivatives2016In: ACS CHEMICAL NEUROSCIENCE, ISSN 1948-7193, Vol. 7, no 12, 1698-1705 p.Article in journal (Refereed)
    Abstract [en]

    Positron emission tomography (PET) tracers play an important role in the diagnosis of Alzheimer's disease, a condition that leads to progressive dementia and memory loss. A high binding affinity and specificity of the PET tracers to amyloid oligomers and fibrils are crucial for their successful application as diagnostic agents. In this sense, it is essential to design PET tracers with enhanced binding affinities, which can lead to more precise and earlier detection of Alzheimer's disease conditions. The application of in silico methodology for the design and development of efficient PET tracers may serve as an important route to improved Alzheimer's disease diagnosis. In this work, the performance of widely used computational methods is explored for predicting experimental binding affinities of styrylbenzoxazole (SB) derivatives against a common amyloid protofibril. By performing docking, molecular dynamics, and quantum chemistry calculations in sequence their combined predictive performance is explored. The present work emphasizes the merits as well as limitations of these simulation strategies in the realm of designing PET tracers for Alzheimer's disease diagnosis.

  • 7. Bednarska, Joanna
    et al.
    Zalesny, Robert
    Murugan, N. Arul
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Bartkowiak, Wojciech
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Odelius, Michael
    Elucidating the Mechanism of Zn2+ Sensing by a Bipyridine Probe Based on Two-Photon Absorption2016In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 120, no 34, 9067-9075 p.Article in journal (Refereed)
    Abstract [en]

    In this work, we examine, by means of computational methods, the mechanism of Zn2+ sensing by a bipyridine-centered, D-pi-A-pi-D-type-ratiometric molecular probe. According to recently published experimental data [Divya, K. P.; Sreejith, S.; Ashokkumar, P.; Yuzhan, K.; Peng, Q; Maji, S. K.; Tong, Y.; Yu, H.; Zhao, Y.; Ramamurthy, P.; Ajayaghosh, A. A ratiometric fluorescent molecular -probe with enhanced two-photon response upon Zn2+ binding for in vitro and in vivo: bioimaging.= Chem. Sci. 2014, S, 3469-3474], after coordination to zinc ions the -probe exhibits a large enhancement of the two -photon absorption cross section. The goal of our investigation was to elucidate the mechanism behind this phenomenon. For this purpose, linear and nonlinear optical properties of -the unbound (cation-free) and bound probe were calculated, including the influence of solute Solvent interactions, implicitly using a polarizable continuum model and exp-licitely employing the QM/MM approach. Because the results of the calculations indicate that many conformers of the probe are energetically accessible at room temperature in solution and hence contribute to the Signal, structurepteperty relationships were also taken into account. Results of our simulations-demonstrate that the one-photon absorption bands for both the unbound -and bound forms correspond to the bright pi -> pi* transition to the first excited state; which, on the other hand,. exhibits negligible two-photon activity. On the basis of the results of the quadratic respOnse calculations, we put forward-notion that it is the second excited state that gives the strong signal in the experimental nonlinear spectrum. To explain the differenCes in the two-photon absorption activity for the two lowest-lying excited states and nonlinear response enhancement upon binding, we employed the generalized few -state model including the ground, first, and- second excited states. The analysis of the optical channel suggests that the large two-photon response is due to the coordination -induced increase of the, transition- moment from the first to the second excited state.

  • 8. Bednarska, Joanna
    et al.
    Zalesny, Robert
    Tian, Guangjun
    Natarajan Arul, Murugan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Bartkowiak, Wojciech
    Nonempirical Simulations of Inhomogeneous Broadening of Electronic Transitions in Solution: Predicting Band Shapes in One- and Two-Photon Absorption Spectra of Chalcones2017In: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, no 10, 1643Article in journal (Refereed)
    Abstract [en]

    We have examined several approaches relying on the Polarizable Embedding (PE) scheme to predict optical band shapes for two chalcone molecules in methanol solution. The PE-TDDFT and PERI-CC2 methods were combined with molecular dynamics simulations, where the solute geometry was kept either as rigid, flexible or partly-flexible (restrained) body. The first approach, termed RBMD-PE-TDDFT, was employed to estimate the inhomogeneous broadening for subsequent convolution with the vibrationally-resolved spectra of the molecule in solution determined quantum-mechanically (QM). As demonstrated, the RBMD-PE-TDDFT/QM-PCM approach delivers accurate band widths, also reproducing their correct asymmetric shapes. Further refinement can be obtained by the estimation of the inhomogeneous broadening using the RBMD-PERI-CC2 method. On the other hand, the remaining two approaches (FBMD-PE-TDDFT and ResBMD-PE-TDDFT), which lack quantum-mechanical treatment of molecular vibrations, lead to underestimated band widths. In this study, we also proposed a simple strategy regarding the rapid selection of the exchange-correlation functional for the simulations of vibrationally-resolved one-and two-photon absorption spectra based on two easy-to-compute metrics.

  • 9.
    Chattopadhyaya, Mausumi
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Murugan, N. Arul
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Origin of the Absorption Band of Bromophenol Blue in Acidic and Basic pH: Insight from a Combined Molecular Dynamics and TD-DFT/MM Study2016In: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 120, no 36, 7175-7182 p.Article in journal (Refereed)
    Abstract [en]

    We study the linear and nonlinear optical properties of a well-known acid base indicator, bromophenol blue (BPB), in aqueous solution by employing static and integrated approaches. In the static approach, optical properties have been calculated using time-dependent density functional theory (TD-DFT) on the fully relaxed geometries of the neutral and different unprotonated forms of BPB. Moreover, both closed and open forms of BPB were considered. In the integrated approach, the optical properties have been computed over many snapshots extracted from molecular dynamics simulation using a hybrid time-dependent density functional theory/molecular mechanics approach. The static approach suggests closed neutral double right arrow anionic interconversion as the dominant mechanism for the red shift in the absorption spectra of BPB due to a change from acidic to basic pH. It is found by employing an integrated approach that the two interconversions, namely open neutral double right arrow anionic and open neutral double right arrow dianionic, can contribute to the pH- dependent shift in the absorption spectra of BPB. Even though both static and integrated approaches reproduce the pH-dependent red shift in the absorption spectra of BPB, the latter one is suitable to determine both the spectra and spectral broadening. Finally, the computed static first hyperpolarizability for various protonated and deprotonated forms of BPB reveals that this molecule can be used as a nonlinear optical probe for pH sensing in addition to its highly exploited use as an optical probe.

  • 10. Chattopadhyaya, Mausumi
    et al.
    Natarajan Arul, Murgan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Alam, Md. Mehboob
    Chakrabarti, Swapan
    Spatial spin-charge separation in neutral endohedral metallofullerene: A combined restricted open-shell MP2 and Car-Parrinello molecular dynamics study2013In: Chemical Physics Letters, ISSN 0009-2614, E-ISSN 1873-4448, Vol. 557, 71-75 p.Article in journal (Refereed)
    Abstract [en]

    We present the first theoretical evidence of the unusual separation of spin and charge degrees of freedom of electron in a neutral endohedral metallofullerene, Sc@C-50. To demystify its origin, we have performed computation at the level of ROMP2 in combination with Car-Parrinello molecular dynamics at 300 K on a series of Sc@C-n. Our inspection reveals that a sharp fall of electron correlation in Sc@C-50 makes the system so sensitive that, to avoid additional Pauli repulsion, Sc leaves the charge component of the solitary 3d electron to C-50 keeping the spin density over its own.

  • 11.
    de Almeida, Katia Júlia
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Natarajan Arul, Murugan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Hugosson, Håkan Wilhelm
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Vahtras, Olav
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Cesar, Amary
    Universidade Federal de Minas Gerais, Departamento de Química.
    Conformations, structural transitions and visible near-infrared absorption spectra of four-, five- and six-coordinated Cu(II) aqua complexes2009In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 11, no 3, 508-519 p.Article in journal (Refereed)
    Abstract [en]

    We have performed Car-Parrinello molecular dynamics simulations at ambient conditions for four-, five- and six-coordinated Cu(II) aqua complexes. The molecular geometry has been investigated in terms of Cu-O, Cu-H bond lengths and O-Cu-O bond angles and compared with earlier experimental measurement results and theoretical calculations. We find that the average Cu-O and Cu-H bond lengths increase with increasing coordination number. We have also observed relatively faster structural transition in the case of five- coordinated complex between trigonal bipyramidal and square pyramidal geometry. This result deviates from the findings of the earlier report (A. Pasquarello et al., Science, 2001, 291, 856) on copper( II) in aqueous solution and we attribute these differences to the neglect of solvent environment in our calculations. The averaged absorption spectra for the copper( II) aqua complexes have been computed using spin-restricted density functional linear response formalism taking 100 snap shots from a trajectory of 0.48 ps. We find that the calculated spectra are significantly different, showing clear features that distinguish each coordination model. Comparison with the experimentally reported absorption spectra is made wherever it is possible and the results obtained favor the distorted fivefold-coordination arrangement for the molecular structure of the Cu(II) ion in aqueous solution.

  • 12.
    Frecus, Bogdan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Natarajan Arul, Murugan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Vahtras, Olav
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Kongsted, Jacob
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    EPR spin Hamiltonian parameters of encapsulated spin-labels: impact of the hydrogen bonding topology2013In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 15, no 7, 2427-2434 p.Article in journal (Refereed)
    Abstract [en]

    Encapsulation of spin-labels into "host'' compounds, like cucurbit[n]urils or cyclodextrins, in solutions has profound effects on the EPR spin Hamiltonian parameters of the spin-labels. In this work we study the microscopic origin of the EPR spin Hamiltonian parameters of spin-labels enclosed in hydrophobic cavities. We focus on the dependence of the EPR properties of encapsulated spin-labels on the hydrogen bonding topologies that occur upon encapsulation, and quantize various contributions to these parameters according to specific hydrogen bonding patterns. The obtained results provide refined insight into the role of the hydrogen bonding induced encapsulation shifts of EPR spin Hamiltonian parameters in solvated "spin-label@host compound'' complexes.

  • 13.
    Harczuk, Ignat
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Murugan, N. Arul
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Vahtras, Olav
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Agren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Studies of pH-Sensitive Optical Properties of the deGFP1 Green Fluorescent Protein Using a Unique Polarizable Force Field2014In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 10, no 8, 3492-3502 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this study is to identify the responsible molecular forms for the pH dependent optical properties of the deGFP1 green fluorescent protein mutant. We have carried out static and dynamic type calculations for all four protonation states of the chromophore to unravel the contributions due to finite temperature and the flexible protein backbone on the pH dependent optical properties. In particular, we have used a combined molecular dynamics and density functional molecular mechanics linear response approach by means of which the optical property calculations were carried out for the chromophore in the explicitly treated solvent and bioenvironment. Two different models were used to describe the environment electronic embedding and polarizable electronic embedding accounting for the polarization of the chromophore and the mutual polarization between the chromophore and the environment, respectively. For this purpose a polarizable force field was derived quantum mechanically for the protein environment by use of analytical response theory. While the gas-phase calculations for the chromophore predict that the induced red shift going from low to high pH is attributed to the change of molecular forms from neutral to zwitterionic, the two more advanced models that explicitly account for the protein backbone attribute the pH shift to a neutral to anionic conversion. Some ramifications of the results for the use of GFPs as pH sensors are discussed.

  • 14. Hede, Thomas
    et al.
    Murugan, Natarajan Arul
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Kongsted, Jacob
    Leck, Caroline
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Simulations of Light Absorption of Carbon Particles in Nanoaerosol Clusters2014In: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 118, no 10, 1879-1886 p.Article in journal (Refereed)
    Abstract [en]

    Black carbon soot (BS) is considered to be the second most contributing organic matter next to carbon dioxide for the global warming effect. There is, however, so far no consensus on the quantitative warming effect due to the increased distribution of black carbon in the atmosphere. A recent report (Science 2012, 337, 1078) suggests that due to BS there is only a few percentage enhancement in absorption of BS-immersed aerosols. To get proper interpretation of the available experimental data, it becomes essential to obtain details of the microscopic origin of the absorption and scattering processes of the aerosol clusters due to the presence of soot. However, so far, due to the large spatial scale and the need for a quantum mechanical description of the particles involved in the absorption and scattering, this quest has posed an insurmountable challenge. In the present work we propose the use of a multiscale integrated approach based on molecular dynamics and a quantum mechanical molecular mechanical method to model the optical property of molecules immersed in nanosized aerosol particles. We choose fluoranthene (FA) with varying cis-pinonic acid (CPA) impurity concentration as an illustrative example of application. We observe that normally FA tends to be on the surface of the nanoaerosols but in the presence of CPA impurities its spatial location changes to a core aggregate to some extent. We find that the absorption maximum is only slightly red-shifted in the presence of increased CPA concentrations and that the oscillator strengths are not altered significantly. The comparable values for the oscillator strengths of all the low energy excitations suggest that the absorption enhancement of the aerosol due to BS will not be substantial, which is in line with the recent experimental report in Science.

  • 15.
    Jena, Naresh K.
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Lyne, ÅL.
    Natarajan Arul, Murugan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Birgisson, B.
    Atomic level simulations of the interaction of asphaltene with quartz surfaces: role of chemical modifications and aqueous environment2017In: Materials and Structures, ISSN 1359-5997, E-ISSN 1871-6873, Vol. 50, no 1, 99Article in journal (Refereed)
    Abstract [en]

    Understanding the properties of bitumen and its interaction with mineral aggregates is crucial for future strategies to improve roads and highways. Knowledge of basic molecular and electronic structures of bitumen, one out of the two main components of asphalt, poses a major step towards achieving such a goal. In the present work we employ atomistic simulation techniques to study the interaction of asphaltenes, a major constituent of bitumen, with quartz surfaces. As an effective means to tune adhesion or cohesion properties of asphaltenes and mineral surfaces, we propose chemical modification of the pristine asphaltene structure. By the choice of substituent and site of substitution we find that adhesion between the asphaltene molecule and the quartz surface can easily be improved at the same time as the cohesive interaction between the asphaltene units is reduced, while other substituents may lead to the opposite effect. We also provide insight at the molecular level into how water molecules affect interactions between asphaltenes and quartz. Our approach emphasizes a future role for advanced atomistic modeling to understand the properties of bitumen and suggest further improvements.

  • 16. Jena, Naresh K.
    et al.
    Murugan, Natarajan Arul
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Solvent-Dependent Conformational States of a [2]Rotaxane-Based Molecular Machine: A Molecular Dynamics Perspective2013In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 117, no 47, 25059-25068 p.Article in journal (Refereed)
    Abstract [en]

    Motion is an essential and fundamental feature of any living organism. The evolved organisms have developed sophisticated and perfect machineries and highly delicate mechanisms to carry out directional and coordinated movements which eventually lead to motion at the macroscopic length scale. By mimicking these natural machineries, attempts to design and synthesize similar molecular motors are made in relevance to their applications in drug delivery, data storage, and molecular sensing. It is highly desirable to establish the rules for controlling the conformational states of molecular motors by tuning some of the external variables which can be used for the design strategies. We contribute to this subject by looking into the solvent influence on the conformational states of a synthetic molecular rotor, namely, diketopyrrolopyrrole (DPP) based [2]rotaxane, using the force-field molecular dynamics approach. We study this system in three different solvents, and we report a strong solvent dependence in the population of three different translational isomers. In chloroform solvent we report the dominant population of the 2-P isomer which is in excellent agreement with experimental results based on H NMR spectra (Org. Lett. 2013, 15, 1274). However, there is a striking difference seen in the population of translational isomers in DMSO solvent, and we attribute these features to negligence of solvent hydrogen bonding induced upfield and downfield effects in the interpretation of experimental proton NMR spectra. In addition, we also report a solvent-polarity-induced fully unstretched to folded conformational transition in the [2]rotaxane system. On the basis of the molecular mechanics Poisson-Boltzmann (and generalized Born) surface area approach, we identify the driving force for the formation of the supramolecular guest-host [2]rotaxane system. Finally, we calculate the relative binding free energies for the macrocycle at different binding sites of the DPP skeleton using the molecular dynamics simulations performed for the macrocycle-rotaxane system in water solvent which suggests the increased stability of the 2-O isomer in polar solvent.

  • 17.
    Kayathri, Rajarathinam
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Murugan, Natarajan Arul
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Premkumar, Albert
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    A plant alkaloid, azadirachtin as an inhibitor for glutathione-S-transferase from Proteus mirabilisArticle in journal (Other academic)
  • 18.
    Kayathri, Rajarathinam
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Murugan, Natarajan Arul
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Palmatine, a nucleotide sequence specific inhibitor for cancer therapyManuscript (preprint) (Other academic)
  • 19.
    Kuang, Guanglin
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Murugan, N. Arul
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Tu, Yaoquan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Nordberg, Agneta
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Investigation of the Binding Profiles of AZD2184 and Thioflavin T with Amyloid-beta(1-42) Fibril by Molecular Docking and Molecular Dynamics Methods2015In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 119, no 35, 11560-11567 p.Article in journal (Refereed)
    Abstract [en]

    Detecting deposits of amyloid beta fibrils in the brain is of paramount importance for an early diagnosis of Alzheimer's disease. A number of PET tracers have been developed for amyloid imaging, but many suffer from poor specificity and large signal to background ratio. Design of tracers with specificity and improved binding affinity requires knowledge about various potential binding sites in the amyloid beta fibril available for the tracers and the nature of the local microenvironment of these sites. In this study we investigate the local structure of fibrils using two important probes, namely, thioflavin T (a fluorescent probe) and AZD2184 (a PET tracer). The target structures for amyloid-beta(1-42) fibril are based on reported NMR solution models. By explicitly considering the effect of fibril flexibility on the available binding sites for all these models, the binding affinity of these probes has been investigated. The binding profiles of AZD2184 and thioflavin T were studied by molecular docking and molecular dynamics simulation methods. The two compounds were found to bind at the same sites of the fibril: three of which are within the fibril, and one is on the two sides of the Met35 residue on the surface. The binding affinity of AZD2184 and thioflavin T is found to be higher at the core sites than on the surface due to more contact residues. The binding affinity of AZD2184 is much higher than that of thioflavin T at every site due to electrostatic interaction and spatial restriction, which is in good agreement with experimental observation. However, the structural change of thioflavin T is much more significant than that of AZD2184, which is the chemical basis for its usage as a fluorescent probe. The ramifications of these results for the design and optimization of PET radioligands and fluorescent probes are briefly discussed.

  • 20.
    Li, Xin
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Kongsted, Jacob
    Natarajan Arul, Murugan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Binding Mechanism and Magnetic Properties of a Multifunctional Spin Label for Targeted EPR Imaging of Amyloid Proteins: Insight from Atomistic Simulations and First-Principles Calculations2012In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 8, no 11, 4766-4774 p.Article in journal (Refereed)
    Abstract [en]

    Electron paramagnetic resonance (EPR) imaging techniques provide a promising approach to detect amyloid structures which are of paramount importance in early-stage diagnosis of conformational diseases. Here, we report a combined molecular dynamics and density functional theory/molecular mechanics computational scheme for evaluation of the binding mechanism between a multifunctional spin label and the target amyloid protein. In addition, we consider evaluation of EPR spin Hamiltonian parameters with the aim of providing a better microscopic understanding and interpretation of EPR spectroscopy. The results from molecular dynamics simulations suggest that the oligothiophene conjugate part of the spin label interacts with hydrophobic residues of the amyloid protein through hydrophobic attraction and that both the N-O bond length and the N-O out-of-plane tilt angle in the nitroxide group are slightly diminished after, complexation with the protein. The translational and rotational motions of the protein bound spin label are considerably slowed compared to those of the free spin label in aqueous solution, but interestingly, hydrogen bonds formed between the nitroxide oxygen group and the surrounding water molecules are hardly affected by the presence Of the amyloid protein. First principles calculation's suggest that EPR spin Hamiltonian parameters including the nitroxide nitrogen hyperfine coupling tensor A(N) and electronic g tensor suffer noticeable changes upon complexation with the protein. The magnitude of the A(N) tensor is found,to:be. closely related to the nitroxide N-O out tilt angle, while the g tensor is affected by both the nitroxide N-O bond length as well as the interaction between the spin label and the amyloid protein With this work we show that state-of-the-art simulation techniques represent a promising way of providing a detailed understanding of the microscopic mechanisms responsible for the formation and stability of a spin label complexed with amyloid structures as well as the magnetic properties of the free and protein-bound spin label.

  • 21. List, Nanna Holmgaard
    et al.
    Zalesny, Robert
    Murugan, N. Arul
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Kongsted, Jacob
    Bartkowiak, Wojciech
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Relation between Nonlinear Optical Properties of Push-Pull Molecules and Metric of Charge Transfer Excitations2015In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 11, no 9, 4182-4188 p.Article in journal (Refereed)
    Abstract [en]

    We establish the relationships between the metric of charge transfer excitation (Delta r) for the bright pi pi* state and the two-photon absorption probability as well as the first hyperpolarizability for two families of push pull pi-conjugated systems. As previously demonstrated by Guido et al. (J. Chem. Theory Comput. 2013, 9, 3118-3126), Delta r is a measure for the average hole electron distance upon excitation and can be used to discriminate between short- and long-range electronic excitations. We indicate two new benefits from using this metric for the analyses of nonlinear optical properties of push pull systems. First, the two-photon absorption probability and the first hyperpolarizability are found to be interrelated through Delta r; if, beta similar to (Delta r)(k), then roughly, delta(TPA) similar to (Delta r)(k+1). Second, a simple power relation between Delta r and the molecular hyperpolarizabilities of push pull systems offers the possibility of estimating properties for longer molecular chains without performing calculations of high-order response functions explicitly. We further demonstrate how to link the hyperpolarizabilities with the chain length of the push-pull pi-conjugated systems through the metric of charge transfer.

  • 22. Matczyszyn, Katarzyna
    et al.
    Olesiak-Banska, Joanna
    Nakatani, Keitaro
    Yu, Pei
    Murugan, Natarajan Arul
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Zalesny, Robert
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology. Wrocław University of Technology, Poland .
    Roztoczynska, Agnieszka
    Bednarska, Joanna
    Bartkowiak, Wojciech
    Kongsted, Jacob
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Samoc, Marek
    One- and Two-Photon Absorption of a Spiropyran-Merocyanine System: Experimental and Theoretical Studies2015In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 119, no 4, 1515-1522 p.Article in journal (Refereed)
    Abstract [en]

    We report on the nonlinear optical properties measurements and quantum-chemical calculations of a well-known photochromic system consisting of spiropyran and the merocyanine photoproduct. The study of nonlinear absorption and refraction properties of the molecules dissolved in chloroform were performed with the Z-scan technique, using femtosecond pulses in a wide range of wavelengths. Maxima in the two-photon absorption spectrum at 700 and 1050 nm were found for the merocyanine form, and the corresponding two-photon absorption cross section is 80 GM and 20 GM, respectively. The latter feature does not vanish completely in the nonlinear spectrum of the spiropyran form, possibly because of the existence of some photoconversion caused by the laser beam during the measurements. A nonlinear absorption peak at 900 nm is found in the spiropyran form with an effective cross section of about 20 GM; it is likely due to three-photon absorption or to absorption by some intermediate species. The experimental data are supported by calculations performed with the use of a hybrid quantum mechanics-molecular mechanics approach.

  • 23. Mudedla, S. K.
    et al.
    Singam, E. R. Azhagiya
    Sundar, J. Vijay
    Pedersen, Morten N.
    Murugan, N. Arul
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Kongsted, Jacob
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Subramanian, V.
    Enhancement of Internal Motions of Lysozyme through Interaction with Gold Nanoclusters and its Optical Imaging2015In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 119, no 1, 653-664 p.Article in journal (Refereed)
    Abstract [en]

    Understanding the interaction of gold nanoclusters with proteins has important ramifications in various fields. We present a study of the interaction between gold nanoclusters and lysozyme investigated using classical molecular dynamics and center-of-mass pulling simulations. The results reveal that the gold nanoclusters induce significant structural changes in lysozyme. Because the internal motions of lysozyme are related to its function, the changes in these internal motions have been quantified using principal component analysis of the molecular dynamics trajectories. The internal motions of lysozyme that are important for its function have been altered because of the interaction with the gold nanocluster. We have also explored how these induced changes in the lysozyme structure affect specific optical properties of the gold nanocluster using the complex polarization propagator method within the time-dependent density functional theory framework, which is of relevance for studies of the optical imaging of lysozyme using gold nanoclusters as molecular probes.

  • 24.
    Murugan, N. Arul
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Solvatochromism in a Pyridinium Cyclopentadienylide: Insights from a Sequential Car-Parrinello QM/MM and TD-DFT/Semicontinuum Approach2014In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 118, no 26, 7358-7366 p.Article in journal (Refereed)
    Abstract [en]

    Understanding the working mechanism and establishing structure-property relationships for optical probes is an essential step to develop design principles for novel molecular probes. Here we study optical properties of a small-sized dielectric probe, namely, 4-carbamido pyridinium cydopentadienylide (CPYC) in benzene and in water solvents using a sequential approach. In particular, the structure modeling has been carried out using a Car-Parrinello hybrid QM/MM molecular dynamics approach, while the excitation energies were computed using time dependent density functional theory. To incorporate the solvent effect either a polarizable continuum model or a semicontinuum description was employed. The molecular dipole moment of CPYC in water is more than two times larger than in benzene solvent. The positive and negative charges tend to accumulate on pyridinium and cyclopentadienylide rings, respectively, with increasing solvent polarity. Significant solvent-induced geometrical changes have been reported in CPYC and this contributes to a significant red shift in spectra. Even though the absorption maxima for CPYC in benzene and water solvents were underestimated, the solvatochromic shift has been reproduced in good agreement with experiments. We also report that CPYC can be used as a two photon probe.

  • 25.
    Murugan, N. Arul
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Halldin, Christer
    Nordberg, Agneta
    Langstrom, Bengt
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    The Culprit Is in the Cave: The Core Sites Explain the Binding Profiles of Amyloid-Specific Tracers2016In: Journal of Physical Chemistry Letters, ISSN 1948-7185, E-ISSN 1948-7185, Vol. 7, no 17, 3313-3321 p.Article in journal (Refereed)
    Abstract [en]

    The design of molecular probes and tracer molecules with specificity toward amyloid beta (A beta) fibrils is of paramount importance for the selective diagnosis of Alzheimer's disease. This requires a detailed understanding of the binding sites in amyloid targets, their number, and their binding mechanism for various tracer molecules. We adopt an integrated approach including molecular docking, molecular dynamics, and generalized Born-based free energy calculations to investigate site-specific interactions of different amyloid binding molecules. Our study reproduces the experimental results on the relative binding affinity of the tracers and amyloid binders and explains the feature of "multiple binding sites" in amyloid targets as probed by competition binding experiments. A major outcome of this study is that it is the core sites of the Afi fibrils that are responsible for the experimentally reported binding profiles of tracers in amyloid targets rather than the surface sites that received much focus in earlier investigations.

  • 26.
    Murugan, N. Arul
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Schrader, Sigurd
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Role of Protonation State and Solvation on the pH Dependent Optical Properties of Bromocresol Green2014In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 10, no 9, 3958-3968 p.Article in journal (Refereed)
    Abstract [en]

    pH sensors play a key role in many industrial and diagnostic applications. Mostly their usage is based on experience, and in many cases the working mechanisms of these sensors are not known in detail, thereby hindering a systematic improvement of such sensors for specific applications. In this report, we present results from combined quantum chemical and molecular mechanics calculations of molecular structures and optical absorption properties of bromocresol green (BRG) in aqueous solution with varying pH value. In the acidic pH range, this chromophore has an intense band with absorption maximum at 444 nm and in the basic pH regime the absorption spectra show a redshift toward 613 nm. In order to identify the molecular structures responsible for this pH dependent optical behavior the closed and open forms of BRG are studied using static approaches considering in each case the three possible protonated states namely, neutral, anionic, and dianionic. For the most significant forms, i.e. the open forms of BRG, extensive modeling based on the integrated approach has been carried out, where the structure and dynamics were studied using hybrid QM/MM molecular dynamics, while the excitation energy calculations were carried out using time dependent density functional theory wherein the surrounding solvent was described as polarizable continuum, semicontinuum, or via a molecular mechanics force-field. The anionic and dianionic forms of BRG have been recognized as molecular forms responsible for its acidic and basic pH behavior, respectively. In contrast to the case of solvatochromic probes, the different protonation states determine the optical behavior in different pH values for pH probes. Hence, the level of solvent description appears to be of minor importance. Independent of the level of theory used to describe the solvent, all models reproduce the spectral features of BRG in different pH and also the pH induced redshift in good agreement with experiment.

  • 27.
    Murugan, N. Arul
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Zalesny, Robert
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology. Wroclaw Univ Technol, Poland.
    Kongsted, Jacob
    Nordberg, Agneta
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Promising two-photon probes for in vivo detection of beta amyloid deposits2014In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 50, no 79, 11694-11697 p.Article in journal (Refereed)
    Abstract [en]

    Based on electronic structure calculations we propose that particular small-sized organic molecules - donor-acceptor substituted phenyl polymethines - can be used as two-photon diagnostic probes for non-invasive imaging of amyloid oligomers and fibrils, which are often referred to as the "early signatures'' of Alzheimer's disease.

  • 28.
    Murugan, Natarajan Arul
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Kongsted, Jacob
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    pH-Induced Modulation of One- and Two-Photon Absorption Properties in a Naphthalene-Based Molecular Probe2013In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 9, no 8, 3660-3669 p.Article in journal (Refereed)
    Abstract [en]

    Presently, there is a great demand for small probe molecules that can be used for two-photon excitation microscopy (TPM)-based monitoring of intracellular and intraorganelle activity and pH. The candidate molecules should ideally possess a large two-photon absorption cross section with optical properties sensitive to pH changes. In the present work, we investigate the potential of a methoxy napthalene (MONAP) derivative for its suitability to serve as a pH sensor using TPM. Using an integrated approach rooted in hybrid quantum mechanics/molecular mechanics, the structures, dynamics, and the one- and two-photon properties of the probe in dimethylformamide solvent are studied. It is found that the protonated form is responsible for the optical property of MONAP at moderately low pH, for which the calculated pH-induced red shift is in good agreement with experiments. A 2-fold increase in the two-photon absorption cross section in the IR region of the spectrum is predicted for the moderately low pH form of the probe, suggesting that this can be a potential probe for pH monitoring of living cells. We also propose some design principles aimed at obtaining control of the absorption spectral range of the probe by structural tuning. Our work indicates that the integrated approach employed is capable of capturing the pH-induced changes in structure and optical properties of organic molecular probes and that such in silico tools can be used to draw structure-property relationships to design novel molecular probes suitable for a specific application.

  • 29.
    Murugan, Natarajan Arul
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Zalesny, Robert
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Kongsted, Jacob
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Chelation-Induced Quenching of Two-Photon Absorption of Azacrown Ether Substituted Distyryl Benzene for Metal Ion Sensing2014In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 10, no 2, 778-788 p.Article in journal (Refereed)
    Abstract [en]

    Imaging of metal ion concentration, distribution, and dynamics can pave the way to diagnose a number of diseases and to identify the normal functioning of the human body. Recently, two-photon microscopy-based imaging of metal ions has become popular due to several favorable factors as compared to fluorescence-based imaging. However, much has to be investigated in order to design probes with large two-photon absorption cross sections and yet with selective binding affinity toward metal ions. In particular, it is crucial to recognize the mechanisms of metal ion-induced changes of the two-photon absorption intensity. The present paper contributes to this effort and reports on the results of extensive studies carried out to define a reliable computational protocol that can account for sampling, solvent, and finite temperature,effects for one- and two-photon properties of metal probes, using azacrown ether substituted distyrylbenzene embedded in solvents as a testbed. We employ a selection of theoretical approaches to model the structure of the probe alone and in the presence of Mg2+ ion in acetonitrile solvent, including static quantum-chemical calculations, rigid- and flexible-body molecular dynamics, and hybrid QM/MM molecular dynamics. For a set of solute-solvent configurations, the one- and the two-photon properties are computed using the recently developed polarizable embedding response approach. It is found that the hybrid QM/MM molecular dynamics based approach is the most successful one among other employed computational strategies, viz, reproduction of the metal ion-induced blue shift in the absorption wavelength and decrease in the two-photon absorption cross section, which actually is in excellent agreement with experimental data. The mechanism for such metal ion-induced changes in the optical properties is put forward using a few-state model. Possible design principles to tune the two-photon absorption properties of probes are also discussed.

  • 30.
    Natarajan Arul, Murgan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Jha, Prakash Chandra
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Pressure dependence of crystal structure and molecular packing in anthracene2009In: Molecular Physics, ISSN 0026-8976, E-ISSN 1362-3028, Vol. 107, no 16, 1689-1695 p.Article in journal (Refereed)
    Abstract [en]

    Anthracene molecular crystal has been investigated up to a pressure of 10.5 GPa at room temperature using variable shape variable size Monte Carlo simulations in an isothermal-isobaric ensemble. We have reported various structural quantities, such as cell parameters and unit cell volume, as a function of pressure and compared them with the experimental results [J. Chem. Phys. 119, 1078 (2003)]. The pressure dependence of angles , and which describe the relative packing of molecules in the crystal has been calculated. We report that anthracene molecular crystal does not exhibit any first order phase transition up to a pressure of 10.5 GPa which is consistent with the experimental observations by Oehzelt et al. [Phys. Rev. B 66, 174104 (2002)]. The calculated equation of state (EOS) has been fitted to a Murnaghan-type EOS with good agreement. The calculated bulk modulus and the pressure derivative of bulk modulus are 8.2 GPa and 8.9 respectively which are in agreement with the experimentally calculated values.

  • 31.
    Natarajan Arul, Murugan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Modeling Solvatochromism of a Quinolinium Betaine Dye in Water Solvent Using Sequential Hybrid QM/MM and Semicontinuum Approach2011In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 115, no 5, 1056-1061 p.Article in journal (Refereed)
    Abstract [en]

    We have investigated the ambient temperature structure of 1-methyl-8-oxyquinolinium betaine (MOQB) in water solvent and compared to its gas-phase structure. We have employed Car-Parrinello molecular dynamics (CPMD) simulations within hybrid quantum mechanics molecular mechanics (QM/MM) framework to study MOQB in water while CPMD technique has been used for the gas phase. We report significant solvent-induced geometrical changes in MOQB. The dipole moment of MOQB in water is 2 times larger than the gas-phase value. The average absorption spectra calculated from gas-phase configurations using Coulomb attenuated-B3LYP (CAMB3LYP) level of theory is comparable with experimental spectra reported in benzene (lambda(max) = 590 nm), a nonpolar solvent. We have also computed the absorption spectra of MOQB in water solvent using continuum and semicontinuum solvent models. Based on this, we have calculated contributions from solvent-induced geometrical changes, hydrogen bonding, and intermolecular charge transfer to the solvatochromic shift and absorption spectra of MOQB in water. Absorption spectra calculations for MOQB in water with a semicontinuum approach for solvents using CAMB3LYP level of theory excellently reproduce the experimental spectra in water, where the theoretical lambda(max) is 433 nm and the experimental lambda(max) is around 440 nm.

  • 32.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Aidas, Kestutis
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Kongsted, Jacob
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    NMR Spin-Spin Coupling Constants in Polymethine Dyes as Polarity Indicators2012In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 18, no 37, 11677-11684 p.Article in journal (Refereed)
    Abstract [en]

    Herein, we explore the use of spinspin coupling constants (SSCCs) in merocyanine (MCYNE) dyes as indicators of polarity. For this purpose, we use CarParrinello hybrid quantum mechanics/molecular mechanics (QM/MM) to determine the structures of MCYNE in solvents of different polarity, followed by computations of the SSCCs by using QM/MM linear-response theory. The molecular geometry of MCYNE switches between neutral, cyanine-like, and zwitterionic depending on the polarity of the solvent. This structural variation is clearly reflected in the proton SSCCs in the polymethine backbone, which are highly sensitive to the dielectric nature of the environment; this mechanism can be used as a polarity indicator for different microenvironments. This result is highlighted by computing the SSCCs of the MCYNE probe in the cavity of the beta-lactoglobulin protein. The computed SSCCs clearly indicate a non-polar hydrophobic dielectric nature of this cavity.

  • 33.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Apostolov, Rossen Pavlov
    KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC.
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Kongsted, Jacob
    epartment of Physics, Chemistry and Pharmacy, University of Southern Denmark.
    Lindahl, Erik
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics.
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Association dynamics and linear and nonlinear optical properties of an N-acetylaladanamide probe in a POPC membrane2013In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 135, no 36, 13590-13597 p.Article in journal (Refereed)
    Abstract [en]

    Along with the growing evidence that relates membrane abnormalities to various diseases, biological membranes have been acknowledged as targets for therapy. Any such abnormality in the membrane structure alters the membrane potential which in principle can be captured by measuring properties of specific optical probes. There exists by now many molecular probes with absorption and fluorescence properties that are sensitive to local membrane structure and to the membrane potential. To suggest new high-performance optical probes for membrane-potential imaging it is important to understand in detail the membrane-induced structural changes in the probe, the membrane association dynamics of the probe, and its membrane-specific optical properties. To contribute to this effort, we here study an optical probe, N-acetylaladanamide (NAAA), in the presence of a POPC lipid bilayer using a multiscale integrated approach to assess the probe structure, dynamics, and optical properties in its membrane-bound status and in water solvent. We find that the probe eventually assimilates into the membrane with a specific orientation where the hydrophobic part of the probe is buried inside the lipid bilayer, while the hydrophilic part is exposed to the water solvent. The computed absorption maximum is red-shifted when compared to the gas phase. The computations of the two-photon absorption and second harmonic generation cross sections of the NAAA probe in its membrane-bound state which is of its first kind in the literature suggest that this probe can be used for imaging the membrane potential using nonlinear optical microscopy.

  • 34.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Chakrabarti, Swapan
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Solvent Dependence of Structure, Charge Distribution, and Absorption Spectrum in the Photochromic Merocyanine-Spiropyran Pair2011In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 115, no 14, 4025-4032 p.Article in journal (Refereed)
    Abstract [en]

    We have studied the structures and absorption spectra of merocyanine, the photoresponsive isomer of the spiropyran (SP) merocyanine (MC) pair, in chloroform and in water solvents using a combined hybrid QM/MM Car-Parrinello molecular dynamics (CP-QM/MM) and ZINDO approach. We report remarkable differences in the molecular structure and charge distribution of MC between the two solvents; the molecular structure of MC remains in neutral form in chloroform while it becomes charge-separated, zwitterionic, in water. The dipole moment of MC in water is about 50% larger than in chloroform, while the value for SP in water is in between, suggesting that the solvent is more influential than the conformation itself in deciding the dipole moment for the merocyanine spiropyran pair. The calculations could reproduce the experimentally reported blue shift in the absorption spectra of MC when going from the nonpolar to the polar solvent, though the actual value of the absorption maximum is overestimated in chloroform solvent. We find that the CP-QM/MM approach is appropriate for structure modeling of solvatochromic and thermochromic molecules as this approach is able to capture the solvent and thermal-induced structural changes within the solute important for an accurate assessment of the properties.

  • 35.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Dasgupta, I.
    Chakraborty, A.
    Ganguli, N.
    Kongsted, J.
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    How crucial are finite temperature and solvent effects on structure and absorption spectra of Si10?2012In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 116, no 50, 26618-26624 p.Article in journal (Refereed)
    Abstract [en]

    We have investigated finite temperature and solvent effects on the structure, and optical absorption properties of the Si10 cluster, as a model for functionalized clusters used in biomedical applications. Among the many isomers possible for Si10 clusters we have studied tetracapped trigonal prism (TCTP) with C3v symmetry, which previously has been reported to be the global minimum structure, using the Car-Parrinello hybrid QM/MM technique. We observe that Si10 remains to be in the TCTP structure in the gas phase, while in solvents we see dominant population of a distorted TCTP conformer which has a similar structure like TCTP except for one of the surface atoms changing its face center position to the edge. We find that there is frequent conformational transitions between these two structures. In the presence of solvents, the interatomic distances are lowered significantly compared to the case of gas phase. While solvent effects appear not to be very significant for the prediction of the excitation energy in the silicon cluster, we find that temperature effects have a substantial influence on its structure and optical properties.

  • 36.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Hugosson, Håkan Wilhelm
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Solvent Dependence of Conformational Distribution, Molecular Geometry, and Electronic Structure in Adenosine2009In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 113, no 4, 1012-1021 p.Article in journal (Refereed)
    Abstract [en]

    Solvation dynamics of adenosine in water and chloroform solvents under ambient conditions has been investigated using both force-field molecular dynamics (MD) and first-principles Car-Parrinello molecular dynamics (CPMD) calculations. First, the solvent dependence of the equilibria between anti-syn forms, C((3'))-endo-C((2'))-endo conformations, and carbinol group rotamers has been discussed from MD calculations. We find that in both the solvents the adenosine molecule can remain either in anti or syn conformations. But, the anti-syn interconversion occurs relatively faster in water solvent than in chloroform solvent. Because of the relatively larger time scale for the interconversion, anti and syn conformational states of adenosine are studied separately in water and chloroform solvents using CPMD calculations. The dipole moments calculated from CPMD and MD calculations for adenosine in water are significantly larger than in chloroform solvent. On the basis of the CPMD calculations, the syn form of adenosine in water has a larger dipole moment than the anti form. Moreover, the molecular geometry of anti and syn forms of adenosine in these two solvents is reported. We report a remarkable solvent effect on the geometry of the anti form of the adenosine, which is attributed to differences in the intermolecular and intramolecular hydrogen-bonding, stabilization. We also report the solvent effect on the frontier Kohn-Sham orbitals and energy gaps for anti-syn conformational states. Finally, we report the solvation shell structure of adenosine in both the solvents, and we find that the solvent-solute interaction is site-specific in the case of water while in chloroform solvent the interaction is globular isotropic in nature.

  • 37.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Jha, Prakash Chandra
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Ruud, Kenneth
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Solvatochromic shift of phenol blue in water from a combined Car-Parrinello molecular dynamics hybrid quantum mechanics-molecular mechanics and ZINDO approach2010In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 132, no 23, 234508- p.Article in journal (Refereed)
    Abstract [en]

    The present work addresses the solvatochromic shift of phenol blue (PB) dye. For this purpose the results of Car-Parrinello molecular dynamics (CPMD) simulations for PB in gas phase are compared with results obtained for PB in water from CPMD hybrid quantum mechanics-molecular mechanics (CPMD-QM/MM) calculations. The absorption spectra were obtained using the intermediate neglect of differential overlap/spectroscopic-configuration interaction (INDO/CIS) method and were calculated for a multitude of configurations of the trajectory. The calculated lambda(max) for PB in gas phase was found to be about 535 nm, which is considerably lower than the lambda(max) reported for PB in nonpolar solvents. Different solvation shells for PB in water have been defined based on the solute-all-atoms and solvent center of mass radial distribution function (g(r(X-O))). The electronic excitation energies for PB computed in the presence of solvent molecules in an increasing number of solvation shells were calculated in a systematic way to evaluate their contributions to the solvatochrmic shift. The inclusion of solvent molecules in the hydration shell yields a lambda(max) of 640 nm, which contributes to almost 78% of the solvatochromic shift. The inclusion of solvent molecules up to 10 angstrom in the g(r(X-O)) rdf yields a lambda(max) of 670 nm which is in good agreement with the experimentally reported value of 654-684 nm. Overall, the present study suggests that the combined CPMD-QM/MM and INDO-CIS approach can be used successfully to model solvatochromic shifts of organic dye molecules. (C) 2010 American Institute of Physics. [doi:10.1063/1.3436516]

  • 38.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Jha, Prakash Chandra
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Solvation shell structure of cyclooctylpyranone in water solvent and its comparative structure, dynamics and dipole moment in HIV protease2009In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 11, no 30, 6482-6489 p.Article in journal (Refereed)
    Abstract [en]

    We have investigated the solvation structure for cyclooctylpyranone (COP) in water solvent using force-field molecular dynamics (MD) and Car-Parrinello mixed quantum mechanics-molecular mechanics (CPMD) calculations. The MD calculations show that in water solvent COP can exist in two conformational states which differ with respect to the relative orientations of the three rings, namely phenyl, pyranone and cyclooctane. We report the existence of strong orientational preference for the water molecule in the first solvation shell and the orientational preference disappears for solvent molecules beyond the first solvation shell. In order to investigate the confinement effect on the structure, dynamics, charge distribution and dipole moment of COP, we have carried out MD and CPMD calculations for COP within HIV type-1 protease (PR). Interestingly, we do not see any conformational transitions for COP within the protein cavity and it remains as a single conformer. We do see a remarkable effect of confinement on few other torsional degrees of freedom such as gg to tg conformational shift for the propyl group of COP. However, the methyl group rotational dynamics remains similar in the water solvent and in the protein environment. Also, within the protein cavity, the COP molecule is more polarized when compared to water solvent. Static ab initio electronic structure calculations were performed on the COP molecule with varying torsional angle in order to investigate the angle dependence of the molecular volume and energy.

  • 39.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Kongsted, Jacob
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Aidas, Kestutis
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Agren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Modeling the Structure and Absorption Spectra of Stilbazolium Merocyanine in Polar and Nonpolar Solvents Using Hybrid QM/MM Techniques2010In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 114, no 42, 13349-13357 p.Article in journal (Refereed)
    Abstract [en]

    We have performed Car-Parrinello mixed quantum mechanics/molecular mechanics (CP-QM/MM) calculations for stilbazolium merocyanine (SM) in polar and nonpolar solvents in order to explore the role of solute molecular geometry, solvation shell structure, and different interaction mechanisms on the absorption spectra and its dependence on solvent polarity. On the basis of the average bond length values and group charge distributions, we find that the SM molecule remains in a neutral quinonoid form in chloroform (a nonpolar solvent) while it transforms to a charge-separated benzenoid form in water (a polar solvent). Based on a quantum mechanical/molecular mechanical response technique, with different MM descriptions for the water environment, absorption spectra were obtained as averages over configurations derived from the CP-QM/MM simulations. We show that for SM in water the solute polarization plays a major role in predictions of the lambda(max) and solvatochromic shift and that once this effect is included the contributions from solvent polarization and intermolecular charge transfer become less important. For SM in chloroform and water solvents, we have also performed absorption spectra calculations using a polarizable continuum model in order to address its relative performance compared to the QM/MM response technique. In the case of SM in water, our study supports the notion that, in order to predict accurate absorption spectra and solvatochromic shifts, it is important to use a discrete description of the solvent when it, as in water, is involved in site-specific interaction with the solute molecule. The technique is thus shown to outperform the more conventional polarizable continuum model in predicting the solvatochromic shift.

  • 40.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Kongsted, Jacob
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Breakdown of the first hyperpolarizability/bond-length alternation parameter relationship2010In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 38, 16453-16458 p.Article in journal (Refereed)
    Abstract [en]

    We have investigated the dependence of the static first hyperpolarizability on the bond-length alternation (BLA) parameter. Our analysis indicates that the validity of the first hyperpolarizability/BLA parameter relationship is restricted to the no-field, vacuum, limit, while it successively breaks down along with increasing polarity of a surrounding medium, becoming invalid, for instance, in an aqueous solution. This contention is based on a series of TD-DFT, TD-DFT/PCM and hybrid TD-DFT/MM calculations of the first hyperpolarizability for a set of molecular configurations generated from Car-Parrinello hybrid QM/MM simulations of the stilbazolium merocyanine chromophore in chloroform and water solvents, and on a rationalization by means of the two-state model for the first hyperpolarizability. The BLA dependence of the three parameters entering the two-state model is shown to be qualitatively different in vacuum and in solvents. Particularly, in the vacuum case, the difference between ground and excited state dipole moments goes to zero for a vanishing BLA, which is not true in the presence of an aqueous medium. In the aqueous medium, an opposing behavior of the parameters involved in the two-state model results in an almost constant first hyperpolarizability with varying BLA parameter.

  • 41.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Kongsted, Jacob
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Color modeling of protein optical probes2012In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 14, no 3, 1107-1112 p.Article in journal (Refereed)
    Abstract [en]

    We present a strategy for modeling optical probes within heterogeneous environments of restricted dimension. The method is based on a multiphysics approach comprising sequential structure modeling by means of hybrid Car-Parrinello molecular dynamics and property modeling by means of quantum mechanics/molecular mechanics response theory. For demonstration we address the structural and optical properties of nile red within the beta-lacto globulin protein. We consider the cases with the probe situated on the surface or within the cavity of the protein, or embedded in a water solvent. We find the absorption properties of the probe to be highly dependent on its position relative to the protein. Structural rearrangements of the optical probe are found to contribute significantly to these environmental effects.

  • 42.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Kongsted, Jacob
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Demystifying the solvatochromic reversal in Brooker's merocyanine dye2011In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 13, no 4, 1290-1292 p.Article in journal (Refereed)
    Abstract [en]

    Based on hybrid QM/MM simulation techniques, we rationalize the spectacular solvatochromic reversal behavior observed for a stilbazolium merocyanine (SM) called Brooker's merocyanine dye. This solvatochromic reversal is attributed to a change in the solute p-electron distribution from zwitterionic to neutral following the change in solvents from polar to non polar. Based on our calculations, we suggest that a polar solvent, like water, with larger relative permittivity is influential enough to bring the change in molecular structure from neutral to zwitterionic. Our results clearly indicate that SM exists in a neutral molecular structure in non polar solvents like trichloromethane and thereby we suggest that self-aggregation of SM may not occur in this solvent.

  • 43.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Olsen, Jogvan Magnus Haugaard
    Kongsted, Jacob
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Aidas, Kestutis
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Amyloid Fibril-Induced Structural and Spectral Modifications in the Thioflavin-T Optical Probe2013In: Journal of Physical Chemistry Letters, ISSN 1948-7185, E-ISSN 1948-7185, Vol. 4, no 1, 70-77 p.Article in journal (Refereed)
    Abstract [en]

    Motivated by future possibilities to design target molecules for fibrils with diagnostic or therapeutic capability related to amyloidosis diseases, we investigate in this work the dielectric nature of amyloid fibril microenvironments in different binding sites using an optical probe, thioflavin-T (THT), which has been used extensively to stain such fibrils. We study the fibril-environment-induced structural and spectral changes of THT at each binding site and compare the results to the fibril-free situation in aqueous solution. All binding sites are found to show a similar effect with respect to the conformational changes of THT; in the presence of the fibril, its molecular geometry tends to become planarized. However, depending on the dielectric nature of the specific binding site, a red shift, blue shift, or no shift in the absorption spectra of THT is predicted. Interestingly, the experimentally measured red shift in the spectra is seen only when THT binds to one of the core or surface-binding sites. It is found that the dielectric nature of the microenvironment in the fibril is strongly nonhomogeneous.

  • 44.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Modeling Solvatochromism of Nile Red in Water2011In: International Journal of Quantum Chemistry, ISSN 0020-7608, E-ISSN 1097-461X, Vol. 111, no 7-8, 1521-1530 p.Article in journal (Refereed)
    Abstract [en]

    Spurred by the pioneering modeling studies of Sylvio Canuto on absorption spectra and solvatochromic shifts of organic molecules in polar and nonpolar solvents, we report in this work a computational study for the common optical dye probe Nile red (NR) to elucidate the origin of its absorption shift between gas phase and aqueous solution. The Car-Parrinello molecular dynamics (CPMD) technique is used for gas phase NR, whereas for NR in water solvent, a hybrid quantum mechanics-molecular dynamics (CPMD-QM/MM) approach has been utilized. For the configurations obtained from CPMD and CPMD-QM/MM, the absorption spectrum has been calculated using the INDO/CIS method as implemented in the ZINDO program. Different solvation shells for NR in water have been defined based on solute-all-atoms and solvent center of mass radial distribution function (g(r(X-O)) rdf). The electronic excitation energies for these solvation shells were calculated in a systematic way to evaluate their individual contributions. In addition, calculations of absorption spectra were performed for NR (excluding solvent molecules) obtained from CPMD-QM/MM calculations to isolate the contribution to the solvatochromic shift just due to solvent-induced geometrical change. Interestingly, this geometrical change in NR itself contributes as much as 50 nm to the solvatochromic shift. The calculated lambda(max) for gas phase is around 488 nm and is comparable to the values reported for NR in nonpolar solvents, whereas the inclusion of solvent molecules in the hydration shell yields a lambda(max) of 565 nm which contributes to almost 77 nm of the solvatochromic shift. The inclusion of solvent molecules up to the fourth solvation shell in the g(r(X-O)) rdf yields lambda(max) of 596 nm which is in good agreement with the experimentally reported value 593 nm. The change in lambda(max) due to inclusion of the fourth solvation shell is only 1 nm, indicating that the spectrum has converged with respect to the solvent effect. Overall, this study suggests that the combined use of CPMD-QM/MM and ZINDO can be successfully used to model and to interpret solvatochromic and thermochromic behavior of NR and other organic dye molecules.

  • 45.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Solvent Dependence on Bond Length Alternation and Charge Distribution in Phenol Blue: A Car-Parrinello Molecular Dynamics Investigation2009In: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 113, no 17, 4833-4839 p.Article in journal (Refereed)
    Abstract [en]

    Car-Parrinello mixed quantum mechanics/classical mechanics (CP-QM/MM) calculations are performed for phenol blue (PB) in chloroform and water solvents along with Car-Parrinello molecular dynamics (CPMD) calculations on PB in the gas phase. The solvent effect on molecular geometry, particularly of bond length alternation (BLA), has been studied. As reported for similar donor-acceptor polyenic systems, a remarkable solvent effect is seen on the BLA. The calculated BLA parameter suggests that PB is in the neutral form in the gas phase and in chloroform solvent, while in water, it is cyanine-like, which is a Mixture of neutral and zwitterionic resonant forms, something that clarifies the controversial reports on the structure of PB in chloroform. We have also verified that the structures obtained from CPMD and CP-QM/MM calculations are correct by calculating absorption spectra for PB in the gas phase and in chloroform solvent and compared with experimental results. To understand the structure for PB in the gas phase and in water solvent, we have carried out Mayer bond order analysis, supporting that the structure of PB in water is cyanine-like. Moreover. PB in water is found to be much more polarized than that in chloroform solvent. Overall, the present work demonstrates that CP-QM/MM calculations can be used to understand the solvent effects on polyenic and merocyanine-like systems, which are usually difficult to model.

  • 46.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Sayeed, Ahmed
    Thermal behavior of disordered phase of caffeine molecular crystal: Insights from Monte Carlo simulation studies2009In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 130, no 20, 204514- p.Article in journal (Refereed)
    Abstract [en]

    We have studied the thermal behavior of orientationally disordered phase of caffeine molecular crystal using variable shape variable size Monte Carlo simulations in isothermal-isobaric ensemble. We have investigated the structure, especially the nature of orientational disorder of caffeine molecules as a function of temperature in the range of 400-550 K. Experimentally this system is known to undergo a phase transition at 426 K (considered to be an orientational order-disorder transition) and melt at 512 K. Our simulations reproduce these two transitions in excellent agreement with experiment. We find that the in-plane reorientational motion of molecules is restricted to small angles below 425 K, and above this temperature, molecules undergo essentially free rotations in molecular plane, and we find the melting to occur between 525 and 550 K. In the high temperature disordered phase, the disorder is mostly attributable to the in-plane orientational motion of the molecules. The potential energy profile for the in-plane reorientational rotation has six wells as a consequence of specific packing of molecules in the ab crystallographic plane. Also we find considerable out-of-plane reorientational disorder for the molecules in the high temperature disordered phase. We have also studied the structure and orientational disorder of the system that is quenched from 450 to 300 K. We find that in the quenched phase, the molecular orientational arrangement remains partially frozen. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3144878]

  • 47.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    1,2-Dichloroethane in Haloalkane Dehalogenase Protein and in Water Solvent: A Case Study of the Confinement Effect on Structural and Dynamical Properties2009In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 113, no 11, 3257-3263 p.Article in journal (Refereed)
    Abstract [en]

    The structural and dynamical properties of an individual molecule is much affected by changes in a surrounding solvent or protein environment. The focus of the present study is to investigate such changes between proteins and solvents, using as an illustrating example the structure and dynamics of 1,2-dichloroethane (DCE) within haloalkane dehalogenase (HAD) as protein and within water as solvent. We have studied DCE within HAD using Car-Parrinello molecular dynamics calculations in a quantum mechanics/molecular mechanics set-up. We find that the C-Cl bond length is shorter in HAD when compared to solution phase value, whereas the net atomic charges and dipole moment are significantly larger than the solution phase values. In contradiction to the usual trend that molecules in the vicinity of the proteins are less polar, we report the observation that the protein environment indeed polarizes the DCE solute more than the water solvent. Furthermore, within the protein environment we do not observe any conformational transition between gauche and trans conformers, and the DCE remains in the more polar gauche conformer during the entire simulation time scale. However, the trans conformer interconverts to the gauche conformer spontaneously within 0.4 ps, which clearly indicates that the trans conformer is unstable within the HAD protein. In contrast, the scatter diagram of total Kohn-Sham energy and dihedral angle between Cl-C-C-Cl atoms shows that the gauche and trans conformers have comparable energies in water. Overall, the present calculations show the within the protein not only the structure of DCE is altered but also that the conformational interconversion dynamics is affected very much. To investigate the confinement effect on the conformational equilibrium, we have also carried out force-field molecular dynamics calculations which show that the population of trans conformer is significantly lower within the protein when compared to that in water solvent.

  • 48.
    Natarajan Arul, Murugan
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry (closed 20110512).
    Role of Dynamic Flexibility in Computing Solvatochromic Properties of Dye-Solvent Systems: o-Betaine in Water2009In: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 113, no 11, 2572-2577 p.Article in journal (Refereed)
    Abstract [en]

    Car-Parrinello molecular dynamics (CPMD) and Car-Parrinello mixed quantum mechanics/classical mechanics (CP-QM/MM) calculations were performed for o-betaine (OB) in the gas phase and water as solvent to study the solvent dependence on its molecular properties: geometry, charge distribution, and dipole moment. It is found that the molecular geometry in the gas phase is close to the planar structure, while in the water it is a twisted structure. The calculations clearly show that in both the gas phase and water the OB molecule is highly flexible with a large amplitude for the twist angle motion. The average gas-phase dipole moment for OB doubles in water, something that concords with a strong increase of total charge on phenoxide and pyridinium rings. We also investigated the solvatochromic shift in the pi-pi* and n-pi* transitions by carrying out INDO/CIS calculations for the gas-phase and solution-phase configurations obtained from the CPMD and CP-QM/MM calculations with results that are in good agreement with available experimental values (J. Chem. Soc., Perkin Trans. 2 1999, 1, 713). Our work indicates the importance of allowing full structural and dynamic flexibility of dye-solvent systems in predicting their basic solvatochromic properties.

  • 49.
    Niskanen, Johannes
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Natarajan Arul, Murugan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Vahtras, Olav
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Li, Cui
    Monti, Susanna
    Carravetta, Vincenzo
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Hybrid density functional-molecular mechanics calculations for core-electron binding energies of glycine in water solution2013In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 15, no 1, 244-254 p.Article in journal (Refereed)
    Abstract [en]

    We report hybrid density functional theory-molecular mechanics (DFT/MM) calculations performed for glycine in water solution at different pH values. In this paper, we discuss several aspects of the quantum mechanics-molecular mechanics (QM/MM) simulations where the dynamics and spectral binding energy shifts are computed sequentially, and where the latter are evaluated over a set of configurations generated by molecular or Car-Parrinello dynamics simulations. In the used model, core ionization takes place in glycine as a quantum mechanical (QM) system modeled with DFT, and the solution is described with expedient force fields in a large molecular mechanical (MM) volume of water molecules. The contribution to the core electronic binding energy from all interactions within and between the two (DFT and MM) parts is accounted for, except charge transfer and dispersion. While the obtained results were found to be in qualitative agreement with experiment, their precision must be qualified with respect to the problem of counter ions, charge transfer and optimal division of QM and MM parts of the system. Results are compared to those of a recent study [Ottoson et al., J. Am. Chem. Soc., 2011, 133, 3120].

  • 50.
    Okoli, Chuka
    et al.
    KTH, School of Biotechnology (BIO), Industrial Biotechnology.
    Sengottiyan, Selvaraj
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Natarajan Arul, Murugan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Pavankumar, Asalapuram Ramachand
    KTH, School of Biotechnology (BIO), Industrial Biotechnology.
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Kuttuva Rajarao, Gunaratna
    KTH, School of Biotechnology (BIO), Industrial Biotechnology.
    In silico modeling and experimental evidence of coagulant protein interaction with precursors for nanoparticle functionalization2013In: Journal of Biomolecular Structure and Dynamics, ISSN 0739-1102, E-ISSN 1538-0254, Vol. 31, no 10, 1182-1190 p.Article in journal (Refereed)
    Abstract [en]

    The design of novel protein-nanoparticle hybrid systems has applications in many fields of science ranging from biomedicine, catalysis, water treatment, etc. The main barrier in devising such tool is lack of adequate information or poor understanding of protein-ligand chemistry. Here, we establish a new strategy based on computational modeling for protein and precursor linkers that can decorate the nanoparticles. Moringa oleifera (MO2.1) seed protein that has coagulation and antimicrobial properties was used. Superparamagnetic nanoparticles (SPION) with precursor ligands were used for the protein-ligand interaction studies. The molecular docking studies reveal that there are two binding sites, one is located at the core binding site; tetraethoxysilane (TEOS) or 3-aminopropyl trimethoxysilane (APTES) binds to this site while the other one is located at the side chain residues where trisodium citrate (TSC) or Si-60 binds to this site. The protein-ligand distance profile analysis explains the differences in functional activity of the decorated SPION. Experimentally, TSC-coated nanoparticles showed higher coagulation activity as compared to TEOS- and APTES-coated SPION. To our knowledge, this is the first report on in vitro experimental data, which endorses the computational modeling studies as a powerful tool to design novel precursors for functionalization of nanomaterials; and develop interface hybrid systems for various applications.

12 1 - 50 of 70
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