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Natarajan Arul, MuruganORCID iD iconorcid.org/0000-0003-0185-5724
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Publications (10 of 75) Show all publications
Mudedla, S. K., Natarajan Arul, M., Subramanian, V. & Ågren, H. (2019). Destabilization of amyloid fibrils on interaction with MoS2-based nanomaterials. RSC Advances, 9(3), 1613-1624
Open this publication in new window or tab >>Destabilization of amyloid fibrils on interaction with MoS2-based nanomaterials
2019 (English)In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 9, no 3, p. 1613-1624Article in journal (Refereed) Published
Abstract [en]

The present work is motivated by the established concept that the structure and energetics of biomacromolecules can be modulated by confining their dimensions in the nanoscale. In particular, here we use force-field methods to understand the stability of amyloid fibrils at nanostructured interfaces, which can be useful for the development of new therapeutics for Alzheimer's disease. We explore the binding modes and structural properties of fibrils at the interface of molybdenum disulphide nanotubes and the nanosurface using classical molecular dynamics simulations. We find that in general the MoS2 materials induces disruptions in the structure of the amyloid fibrils where the beta sheet conformation of the fibrils changes to a turned conformation, and it is large in the case of nanotubes in comparison to the nanosurfaces. The intermolecular hydrogen bonds, hydrophilic and hydrophobic contacts between the monomer peptides in the fibril are reduced due to their adsorption onto the MoS2 materials, which results in a destabilization of the fibril. The destabilization of fibril is to some extent compensated for by the van der Waals interactions between the fibril and MoS2. Overall the results indicate that MoS2-based materials can be useful in inhibiting the aggregation of smaller protofibrils to matured fibrils and to bust the already formed fibrils. Therapeutic materials should not exhibit any cross interaction with other off-targets compounds. In order to test whether the MoS2 nanomaterial has any such effect we have studied its interaction with two additional biomacromolecules, the human serum albumin and p53 protein, and we report no significant changes in the secondary structure of these biomolecules. Through molecular docking studies we also established that the drug binding ability of HSA is not altered by its surface binding to MoS2 nanosurface.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2019
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-244120 (URN)10.1039/c8ra10184a (DOI)000457292800050 ()2-s2.0-85060139369 (Scopus ID)
Note

QC 20190219

Available from: 2019-02-19 Created: 2019-02-19 Last updated: 2019-02-19Bibliographically approved
Guanglin, K., Murugan, N. A. & Ågren, H. (2019). Mechanistic Insight into the Binding Profile of DCVJ and alpha-Synuclein Fibril Revealed by Multiscale Simulations. ACS Chemical Neuroscience, 10(1), 610-617
Open this publication in new window or tab >>Mechanistic Insight into the Binding Profile of DCVJ and alpha-Synuclein Fibril Revealed by Multiscale Simulations
2019 (English)In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 10, no 1, p. 610-617Article in journal (Refereed) Published
Abstract [en]

Parkinson's disease (PD) is a serious neuro-degenerative disease and is characterized by abnormal alpha-synuclein (alpha-syn) accumulation in Lewy bodies (LB) and 2 Lewy neurites (LN), which makes alpha-syn an important imaging target for PD. An imaging probe that quantifies fibrillar alpha-syn can enhance the clinical diagnosis of PD and can also be used to evaluate the efficacy of therapeutics aimed at reducing the abnormal aggregation of the alpha-syn fibril in the brain. In this paper, we study the binding profile of fibrillar alpha-syn with a fluorescent probe 4-(dicyanovinyl)julolidine (DCVJ), which is being explored for identifying alpha-syn imaging agents. A multiscale simulation workflow including molecular docking, molecular dynamics, metadynamics, and QM/MM calculations was implemented. We find that DCVJ can bind to multiple sites of alpha-syn which are located either at the surface or in the core. Free energy calculations using implicit solvent models reveal that the most favorable binding mode for DCVJ is associated with the core binding site and is further confirmed by metadyamics simulation. Besides, a dynamic binding pathway is discovered, which reveals that DCVJ binds gradually into the core of the fibril passing through several intermediate states. The conformational arrest of the dicyano vinyl group in the fibrillar environment could explain the reason behind the fibril-specific fluorescence of DCVJ. Furthermore, based on hybrid QM/MM calculations, the molecular geometry of the dicyano vinyl group is found to be environment specific which explains why DCVJ serves as a staining agent for such fibrillar-like environments. Our results could be helpful for elucidating the binding mechanism of imaging tracers with the fibrillar form of alpha-syn and explain their fibrillar-specific optical properties, a knowledge that in turn can be used to guide the design and development of compounds with higher affinity and selectivity for alpha-syn using structure-based strategies.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2019
Keywords
alpha-Synuclein, DCVJ, imaging agents, molecular docking, binding free energy calculations, metadynamics
National Category
Theoretical Chemistry
Identifiers
urn:nbn:se:kth:diva-243968 (URN)10.1021/acschemneuro.8b00465 (DOI)000456351300062 ()30277753 (PubMedID)2-s2.0-85055257565 (Scopus ID)
Note

QC 20190301

Available from: 2019-03-01 Created: 2019-03-01 Last updated: 2019-03-01Bibliographically approved
Osella, S., Di Meo, F., Natarajan Arul, M., Fabre, G., Ameloot, M., Trouillas, P. & Knippenberg, S. (2018). Combining (Non)linear Optical and Fluorescence Analysis of DiD To Enhance Lipid Phase Recognition. Journal of Chemical Theory and Computation, 14(10), 5350-5359
Open this publication in new window or tab >>Combining (Non)linear Optical and Fluorescence Analysis of DiD To Enhance Lipid Phase Recognition
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2018 (English)In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 14, no 10, p. 5350-5359Article in journal (Refereed) Published
Abstract [en]

The widespread interest in phase recognition of lipid membranes has led to the use of different optical techniques to enable differentiation of healthy and not fully functional cells. In this work, we show how the combination of different (non)linear optical methods such as one-photon absorption (OPA), two-photon absorption (TPA), and second harmonic generation (SHG) as well as the study of the fluorescence decay time leads to an enhanced screening of membrane phases using a fluorescent 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiD) probe. In the current study we consider the pure liquid disordered phases of DOPC (dioleoyl-sn-glycero-3-phosphocholine, room temperature) and DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 323 K), the solid gel phase of DPPC (298 K), and the liquid ordered phase of a 2:1 binary mixture of sphingomyelin and cholesterol. By means of extensive hybrid quantum mechanics molecular mechanics calculations and based upon the (non)linear absorption of the embedded probes, it is found that DiD can be used to identify the lipid bilayer phase. The joint TPA and SHG as well as fluorescence analyses qualifies DiD as a versatile probe for phase recognition. In particular, the SHG data obtained by means of hyper-Rayleigh scattering and by electric field induced second harmonic generation reveal differences in polarization of the probe in the different environments. The TPA results finally confirm the particular location of the probe in between the polar headgroup region of the 2:1 SM:Chol mixture in the liquid ordered phase.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2018
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-238130 (URN)10.1021/acs.jctc.8b00553 (DOI)000447238500031 ()30216061 (PubMedID)2-s2.0-85054346528 (Scopus ID)
Note

QC 20181113

Available from: 2018-11-13 Created: 2018-11-13 Last updated: 2018-11-13Bibliographically approved
Natarajan Arul, M., Nordberg, A. & Ågren, H. (2018). Different Positron Emission Tomography Tau Tracers Bind to Multiple Binding Sites on the Tau Fibril: Insight from Computational Modeling. ACS Chemical Neuroscience, 9(7), 1757-1767
Open this publication in new window or tab >>Different Positron Emission Tomography Tau Tracers Bind to Multiple Binding Sites on the Tau Fibril: Insight from Computational Modeling
2018 (English)In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 9, no 7, p. 1757-1767Article in journal (Refereed) Published
Abstract [en]

Using the recently reported cryo-EM structure for the tau fibril [Fitzpatrick et al. (2017) Nature 547, 185-190], which is a potential target concerning Alzheimer's disease, we present the first molecular modeling studies on its interaction with various positron emission tomography (PET) tracers. Experimentally, based on the binding assay studies, at least three different high affinity binding sites have been reported for tracers in the tau fibril. Herein, through integrated modeling using molecular docking, molecular dynamics, and binding free energy calculations, we provide insight into the binding patterns of various tracers to the tau fibril. We suggest that there are four different high affinity binding sites available for many of the studied tracers showing varying binding affinity to different binding sites. Thus, PBB3 binds most strongly to site 4, and interestingly, this site is not a preferable site for any other tracers. For THIC5351, our data show that it strongly binds to sites 3 and 1, the former one being more preferable. We also find that MK6240 and T807 bind to site 1 specifically. The modeling data also give some insight into whether a tracer bound to a specific site can be replaced by others or not. For example, the displacement of T807 by PBB3 as reported experimentally can also be explained and attributed to the larger binding affinity of the latter compound in all binding sites. The binding free energy results explain very well the small binding affinity of THK523 compared to all the aryl quinoline moieties containing THK tracers. The ability of certain tau tracers, like FDDNP and THK523, to bind to amyloid fibrils has also been investigated. Furthermore, such off-target interaction of tau tracers with amyloid beta fibrils has been validated using a quantum mechanical fragmentation approach.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-232912 (URN)10.1021/acschemneuro.8b00093 (DOI)000439531400024 ()29630333 (PubMedID)2-s2.0-85050285842 (Scopus ID)
Note

QC 20180808

Available from: 2018-08-08 Created: 2018-08-08 Last updated: 2018-11-13Bibliographically approved
Mudedla, S. K., Natarajan Arul, M. & Ågren, H. (2018). Free Energy Landscape for Alpha-Helix to Beta-Sheet Interconversion in Small Amyloid Forming Peptide under Nanoconfinement. Journal of Physical Chemistry B, 122(42), 9654-9664
Open this publication in new window or tab >>Free Energy Landscape for Alpha-Helix to Beta-Sheet Interconversion in Small Amyloid Forming Peptide under Nanoconfinement
2018 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 122, no 42, p. 9654-9664Article in journal (Refereed) Published
Abstract [en]

Understanding the mechanism of fibrillization of amyloid forming peptides could be useful for the development of therapeutics for Alzheimer's disease (AD). Taking this standpoint, we have explored in this work the free energy profile for the interconversion of monomeric and dimeric forms of amyloid forming peptides into different secondary structures namely beta-sheet, helix, and random coil in aqueous solution using umbrella sampling simulations and density functional theory calculations. We show that the helical structures of amyloid peptides can form beta sheet rich aggregates through random coil conformations in aqueous condition. Recent experiments (Chem. Eur. J. 2018, 24, 3397-3402 and ACS Appl. Mater. Interfaces 2017, 9, 21116-21123) show that molybdenum disulfide nanosurface and nanoparticles can reduce the fibrillization process of amyloid beta peptides. We have unravelled the free energy profile for the interconversion of helical forms of amyloid forming peptides into beta-sheet and random coil in the presence of a two-dimensional nanosurface of MoS2. Results indicate that the monomer and dimeric forms of the peptides adopt the random coil conformation in the presence of MoS2 while the helical form is preferable for the monomeric form and that the beta-sheet and helix forms are the preferable forms for dimers in aqueous solution. This is due to strong interaction with MoS2 and intramolecular hydrogen bonds of random coil conformation. The stabilization of random coil conformation does not lead to a beta sheet like secondary structure for the aggregate. Thus, the confinement of MoS2 promotes deaggregation of amyloid beta peptides rather than aggregation, something that could be useful for the development of therapeutics for AD.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-239093 (URN)10.1021/acs.jpcb.8b07917 (DOI)000448753800004 ()30253649 (PubMedID)2-s2.0-8505500840 (Scopus ID)
Funder
Swedish Foundation for Strategic Research , SNIC2017-12-49Swedish Foundation for Strategic Research , SNIC2018-3-3
Note

QC 20181121

Available from: 2018-11-21 Created: 2018-11-21 Last updated: 2018-11-21Bibliographically approved
Poongavanam, V., Namasivayam, V., Vanangamudi, M., Al Shamaileh, H., Veedu, R. N., Kihlberg, J. & Natarajan Arul, M. (2018). Integrative approaches in HIV-1 non-nucleoside reverse transcriptase inhibitor design. Wiley Interdisciplinary Reviews. Computational Molecular Science, 8(1), Article ID e1328.
Open this publication in new window or tab >>Integrative approaches in HIV-1 non-nucleoside reverse transcriptase inhibitor design
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2018 (English)In: Wiley Interdisciplinary Reviews. Computational Molecular Science, ISSN 1759-0876, E-ISSN 1759-0884, Vol. 8, no 1, article id e1328Article in journal (Refereed) Published
Abstract [en]

The design of inhibitors for human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT) is one of the most successful approaches for the treatment of HIV infections. Among the HIV-1 RT inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs) constitute a prominent drug class, which includes nevirapine, delavirdine, efavirenz, etravirine, and rilpivirine approved for clinical use. However, the efficiency of many of these drugs has been undermined by drug-resistant variants of HIV-1 RT, and it therefore becomes inevitable to design novel drugs to cope with resistance. Here, we discuss various drug design strategies, which include traditional medicinal chemistry, computational chemistry, and chemical biology approaches. In particular, computational modeling approaches, including machine learning, empirical descriptors-based, force-field, ab initio, and hybrid quantum mechanics/molecular mechanics-based methods are discussed in detail. We foresee that these methods will have a major impact on efforts to guide the design and discovery of the next generation of NNRTIs that combat RT multidrug resistance.

National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:kth:diva-220586 (URN)10.1002/wcms.1328 (DOI)000418158400002 ()2-s2.0-85041348314 (Scopus ID)
Note

QC 20180122

Available from: 2018-01-22 Created: 2018-01-22 Last updated: 2018-01-22Bibliographically approved
Zhang, J., Poongavanam, V., Kang, D., Bertagnin, C., Lu, H., Kong, X., . . . Liu, X. (2018). Optimization of N-Substituted Oseltamivir Derivatives as Potent Inhibitors of Group-1 and-2 Influenza A Neuraminidases, Including a Drug-Resistant Variant. Journal of Medicinal Chemistry, 61(14), 6379-6397
Open this publication in new window or tab >>Optimization of N-Substituted Oseltamivir Derivatives as Potent Inhibitors of Group-1 and-2 Influenza A Neuraminidases, Including a Drug-Resistant Variant
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2018 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 61, no 14, p. 6379-6397Article in journal (Refereed) Published
Abstract [en]

On the basis of our earlier discovery of N1-selective inhibitors, the 150-cavity of influenza virus neuraminidases (NAs) could be further exploited to yield more potent oseltamivir derivatives. Among the synthesized compounds, 15b and 15c were exceptionally active against both group-1 and -2 NAs. Especially for 09N1, N2, N6, and N9 subtypes, they showed 6.80-12.47 and 1.20-3.94 times greater activity than oseltamivir carboxylate (OSC). They also showed greater inhibitory activity than OSC toward H274Y and E119V variant. In cellular assays, they exhibited greater potency than OSC toward H5N1, H5N2, H5N6, and H5N8 viruses. 15b demonstrated high metabolic stability, low cytotoxicity in vitro, and low acute toxicity in mice. Computational modeling and molecular dynamics studies provided insights into the role of R group of 15b in improving potency toward group-1 and -2 NAs. We believe the successful exploitation of the 150-cavity of NAs represents an important breakthrough in the development of more potent anti-influenza agents.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:kth:diva-233424 (URN)10.1021/acs.jmedchem.8b00929 (DOI)000440521300038 ()29965752 (PubMedID)2-s2.0-85049659038 (Scopus ID)
Note

QC 20180820

Available from: 2018-08-20 Created: 2018-08-20 Last updated: 2018-08-20Bibliographically approved
Zhang, J., Natarajan Arul, M., Tian, Y., Bertagnin, C., Fang, Z., Kang, D., . . . Liu, X. (2018). Structure-Based Optimization of N-Substituted Oseltamivir Derivatives as Potent Anti-Influenza A Virus Agents with Significantly Improved Potency against Oseltamivir-Resistant N1-H274Y Variant. Journal of Medicinal Chemistry, 61(22), 9976-9999
Open this publication in new window or tab >>Structure-Based Optimization of N-Substituted Oseltamivir Derivatives as Potent Anti-Influenza A Virus Agents with Significantly Improved Potency against Oseltamivir-Resistant N1-H274Y Variant
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2018 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 61, no 22, p. 9976-9999Article in journal (Refereed) Published
Abstract [en]

Due to the emergence of highly pathogenic and oseltamivir-resistant influenza viruses, there is an urgent need to develop new anti-influenza agents. Herein, five subseries of oseltamivir derivatives were designed and synthesized to improve their activity toward drug-resistant viral strains by further exploiting the 150-cavity in the neuraminidases (NAs). The bioassay results showed that compound 21h exhibited antiviral activities similar to or better than those of oseltamivir carboxylate (OSC) against H5N1, H5N2, H5N6, and H5N8. Besides, 21h was 5- to 86-fold more potent than OSC toward N1, N8, and N1-H274Y mutant NAs in the inhibitory assays. Computational studies provided a plausible rationale for the high potency of 21h against group-1 and N1-H274Y NAs. In addition, 21h demonstrated acceptable oral bioavailability, low acute toxicity, potent antiviral activity in vivo, and high metabolic stability. Overall, the above excellent profiles make 21h a promising drug candidate for the treatment of influenza virus infection.

Place, publisher, year, edition, pages
American Chemical Society, 2018
Keywords
4 acetamido 3 (pentan 3 yloxy) 5 [(4 phenoxybenzyl)amino]cyclohex 1 ene 1 carboxylic acid, 4 acetamido 3 (pentan 3 yloxy) 5 [[4 (pentan 3 yloxy)benzyl]amino]cyclohex 1 ene 1 carboxylic acid, 4 acetamido 3 (pentan 3 yloxy) 5 [[4 (phenylsulfonyl)benzyl]amino]cyclohex 1 ene 1 carboxylic acid, 4 acetamido 3 (pentan 3 yloxy) 5 [[4 (phenylthio)benzyl]amino]cyclohex 1 ene 1 carboxylic acid, 4 acetamido 3 (pentan 3 yloxy) 5 [[4 (thiophen 2 yl thio)benzyl]amino]cyclohex 1 ene 1 carboxylic acid, 4 acetamido 5 amino 3 (1 ethylpropoxy) 1 cyclohexene 1 carboxylic acid, 4 acetamido 5 [(4 benzoylbenzyl)amino] 3 (pentan 3 yloxy)cyclohex 1 ene 1 carboxylic acid, 4 acetamido 5 [(4 benzylbenzyl)amino] 3 (pentan 3 yloxy)cyclohex 1 ene 1 carboxylic acid, 4 acetamido 5 [(4 ethylbenzyl)amino] 3 (pentan 3 yloxy)cyclohex 1 ene 1 carboxylic acid, 4 acetamido 5 [(4 isopropylbenzyl)amino] 3 (pentan 3 yloxy)cyclohex 1 ene 1 carboxylic acid, 4 acetamido 5 [(4 methoxybenzyl)amino] 3 (pentan 3 yloxy)cyclohex 1 ene 1 carboxylic acid, 4 acetamido 5 [[3 (cyclopentyl)benzyl]amino] 3 (pentan 3 yloxy)cyclohex 1 ene 1 carboxylic acid, 4 acetamido 5 [[3 (sec butylthio)benzyl]amino] 3 (pentan 3 yloxy)cyclohex 1 ene 1 carboxylic acid, 4 acetamido 5 [[4 (benzo[b]thiophen 2 yl)benzyl)amino] 3 (pentan 3 yloxy)cyclohex 1 ene 1 carboxylic acid, 4 acetamido 5 [[4 (cyclohexylthio)benzyl]amino] 3 (pentan 3 yloxy)cyclohex 1 ene 1 carboxylic acid, 4 acetamido 5 [[4 (cyclopentyl)benzyl]amino] 3 (pentan 3 yloxy)cyclohex 1 ene 1 carboxylic acid, 4 acetamido 5 [[4 (isobutylthio)benzyl]amino] 3 (pentan 3 yloxy)cyclohex 1 ene 1 carboxylic acid, 4 acetamido 5 [[4 (sec butylthio)benzyl]amino] 3 (pentan 3 yloxy)cyclohex 1 ene 1 carboxylic acid, antivirus agent, diclofenac, ethyl 4 acetamido 3 (pentan 3 yloxy) 5 [[4 (phenylthio)benzyl]amino]cyclohex 1 ene 1 carboxylate, ethyl 4 acetamido 5 [[4 (benzo[b]thiophen 5 yl)benzyl]amino] 3 (pentan 3 yloxy) cyclohex 1 ene 1 carboxylate, oseltamivir, oseltamivir derivative, propafenone, ribavirin, testosterone, unclassified drug, unindexed drug, virus sialidase, zanamivir, animal experiment, animal model, antiviral activity, area under the curve, Article, bioassay, controlled study, drug clearance, drug half life, drug potency, drug stability, drug structure, drug synthesis, human, human cell, Influenza A virus, Influenza A virus (H3N2), Influenza A virus (H5N1), Influenza A virus (H5N2), Influenza A virus (H5N6), Influenza A virus (H5N8), maximum concentration, MDCK cell line, metabolic stability, molecular model, nonhuman, pharmacokinetic parameters, plasma concentration-time curve, rat, time to maximum plasma concentration
National Category
Basic Medicine
Identifiers
urn:nbn:se:kth:diva-247045 (URN)10.1021/acs.jmedchem.8b01065 (DOI)000451496300010 ()2-s2.0-85056802789 (Scopus ID)
Note

QC 20190625

Available from: 2019-06-25 Created: 2019-06-25 Last updated: 2019-06-25Bibliographically approved
Natarajan Arul, M., Zalesny, R. & Ågren, H. (2018). Unusual binding-site-specific photophysical properties of a benzothiazole-based optical probe in amyloid beta fibrils. Physical Chemistry, Chemical Physics - PCCP, 20(31), 20334-20339
Open this publication in new window or tab >>Unusual binding-site-specific photophysical properties of a benzothiazole-based optical probe in amyloid beta fibrils
2018 (English)In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 20, no 31, p. 20334-20339Article in journal (Refereed) Published
Abstract [en]

Optical imaging of amyloid fibrils serves as a cost-effective route for the diagnosis of Alzheimer-like conformational diseases. However, the challenge here is to optimize the binding affinity and photophysical properties of the optical imaging agents in a way specific to certain types of amyloids. In a few occasions it is shown that novel optical imaging agents can be designed to bind to a particular type of amyloid fibril with larger binding affinity and specificity. There is also a recent report on photoluminescent polythiophenes which display photophysical properties that can be used to distinguish the variants or subtypes of amyloids (J. Rasmussen et al., Proc. Natl. Acad. Sci. U. S. A., 2017, 114(49), 13018-13023). Based on a multiscale modeling approach, here, we report on the complementary aspect that the photophysical properties of a benzothiazole based optical probe (referred to as BTA-3) can be specific to the binding sites in the same amyloid fibrils and we attribute this to its varying electronic structure in different sites. As reported experimentally from competitive binding assay studies for many amyloid staining molecules and tracers, we also show multiple binding sites in amyloid fibrils for this probe. In particular, BTA-3 displayed a red-shift in its low-frequency absorption band only in site-4, a surface site of amyloid fibrils when compared to the spectra in water solvent. In the remaining sites, it exhibited a less significant blue shift for the same absorption band.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2018
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-234603 (URN)10.1039/c8cp03274b (DOI)000442270800002 ()30043007 (PubMedID)2-s2.0-85051538493 (Scopus ID)
Funder
Swedish Foundation for Strategic Research
Note

QC 20180914

Available from: 2018-09-14 Created: 2018-09-14 Last updated: 2018-09-14Bibliographically approved
Jena, N. K., Lyne, Å., Natarajan Arul, M., Ågren, H. & Birgisson, B. (2017). Atomic level simulations of the interaction of asphaltene with quartz surfaces: role of chemical modifications and aqueous environment. Materials and Structures, 50(1), Article ID 99.
Open this publication in new window or tab >>Atomic level simulations of the interaction of asphaltene with quartz surfaces: role of chemical modifications and aqueous environment
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2017 (English)In: Materials and Structures, ISSN 1359-5997, E-ISSN 1871-6873, Vol. 50, no 1, article id 99Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Kluwer Academic Publishers, 2017
Keywords
Adhesion, Bitumen, Cohesion, Molecular dynamics, Quartz, Bituminous materials, Chemical modification, Electronic structure, Molecules, Aqueous environment, Atomic level simulations, Atomistic modeling, Atomistic simulations, Cohesion properties, Cohesive interactions, Asphaltenes
National Category
Materials Engineering
Identifiers
urn:nbn:se:kth:diva-201948 (URN)10.1617/s11527-016-0880-y (DOI)000405071300013 ()2-s2.0-84994500697 (Scopus ID)
Note

QC 20170306

Available from: 2017-03-06 Created: 2017-03-06 Last updated: 2017-08-01Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-0185-5724

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