Publication:
Large-scale all-atom molecular dynamics alanine-scanning of IAPP octapeptides provides insights into the molecular determinants of amyloidogenicity

dc.contributor.authorTambi, Richa
dc.date.accessioned2021-08-04T07:25:57Z
dc.date.available2021-08-04T07:25:57Z
dc.date.issued2019-02-21
dc.description.abstractAbstract: 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 observationsen_US
dc.identifier.other204-2019.52
dc.identifier.urihttps://repository.mbru.ac.ae/handle/1/416
dc.language.isoenen_US
dc.subjectMolecular dynamicsen_US
dc.subjectIAPP octapeptidesen_US
dc.subjectAmyloidogenicityen_US
dc.titleLarge-scale all-atom molecular dynamics alanine-scanning of IAPP octapeptides provides insights into the molecular determinants of amyloidogenicityen_US
dc.typeArticleen_US
dspace.entity.typePublicationen_US

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