Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Free Energy Landscape for Alpha-Helix to Beta-Sheet Interconversion in Small Amyloid Forming Peptide under Nanoconfinement
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH). AlbaNova Univ Ctr, Royal Inst Technol KTH, Sch Engn Sci Chem Biotechnol & Hlth, Dept Theoret Chem & Biol, S-10691 Stockholm, Sweden..
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Theoretical Chemistry and Biology. AlbaNova Univ Ctr, Royal Inst Technol KTH, Sch Engn Sci Chem Biotechnol & Hlth, Dept Theoret Chem & Biol, S-10691 Stockholm, Sweden..ORCID iD: 0000-0003-0185-5724
KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. AlbaNova Univ Ctr, Royal Inst Technol KTH, Sch Engn Sci Chem Biotechnol & Hlth, Dept Theoret Chem & Biol, S-10691 Stockholm, Sweden.;Uppsala Univ, Dept Phys & Astron, Box 516, SE-75120 Uppsala, Sweden..ORCID iD: 0000-0002-1763-9383
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. Vol. 122, no 42, p. 9654-9664
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:kth:diva-239093DOI: 10.1021/acs.jpcb.8b07917ISI: 000448753800004PubMedID: 30253649Scopus ID: 2-s2.0-8505500840OAI: oai:DiVA.org:kth-239093DiVA, id: diva2:1264862
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

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records BETA

Mudedla, Sathish KumarNatarajan Arul, MuruganÅgren, Hans

Search in DiVA

By author/editor
Mudedla, Sathish KumarNatarajan Arul, MuruganÅgren, Hans
By organisation
School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH)Theoretical Chemistry and BiologyAlbanova VinnExcellence Center for Protein Technology, ProNova
In the same journal
Journal of Physical Chemistry B
Chemical Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 12 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf