Publication: Large-scale all-atom molecular dynamics alanine-scanning of IAPP octapeptides provides insights into the molecular determinants of amyloidogenicity
dc.contributor.author | Tambi, Richa | |
dc.date.accessioned | 2021-08-04T07:25:57Z | |
dc.date.available | 2021-08-04T07:25:57Z | |
dc.date.issued | 2019-02-21 | |
dc.description.abstract | Abstract: In order to investigate the early phase of the amyloid formation by the short amyloidogenic octapeptide sequence (‘NFGAILSS’) derived from IAPP, we carried out a 100ns all-atom molecular dynamics (MD) simulations of systems that contain 27 peptides and over 30,000 water molecules. The large-scale calculations were performed for the wild type sequence and seven alanine-scanned sequences using AMBER 8.0 on RIKEN’s special purpose MD-GRAPE3 supercomputer, using the all-atom point charge force field ff99, which do not favor β-structures. Large peptide clusters (size 18–26 mers) were observed for all simulations, and our calculations indicated that isoleucine at position 5 played important role in the formation of β-rich clusters. In the oligomeric state, the wild type and the S7A sequences had the highest β-structure content (~14%), as calculated by DSSP, in line with experimental observations, whereas I5A and G3A had the highest helical content (~20%). Importantly, the β-structure preferences of wild type IAPP originate from its association into clusters and are not intrinsic to its sequence. Altogether, the results of this first large-scale, multi-peptide all-atom molecular dynamics simulation appear to provide insights into the mechanism of amyloidogenic and non-amyloidogenic oligomers that mainly corroborate previous experimental observations | en_US |
dc.identifier.other | 204-2019.52 | |
dc.identifier.uri | https://repository.mbru.ac.ae/handle/1/416 | |
dc.language.iso | en | en_US |
dc.subject | Molecular dynamics | en_US |
dc.subject | IAPP octapeptides | en_US |
dc.subject | Amyloidogenicity | en_US |
dc.title | Large-scale all-atom molecular dynamics alanine-scanning of IAPP octapeptides provides insights into the molecular determinants of amyloidogenicity | en_US |
dc.type | Article | en_US |
dspace.entity.type | Publication | en_US |