Multiscale Modeling of Amyloid Fibrils Formed by Aggregating Peptides Derived from the Amyloidogenic Fragment of the A-Chain of Insulin.

ABSTRACT: Computational prediction of molecular structures of amyloid fibrils remains an exceedingly challenging task. In this work, we propose a multi-scale modeling procedure for the structure prediction of amyloid fibrils formed by the association of ACC_1-13 aggregation-prone peptides derived from the N-terminal region of insulin's A-chain. First, a large number of protofilament models composed of five copies of interacting ACC_1-13 peptides were predicted by application of CABS-dock coarse-grained (CG) docking simulations. Next, the models were reconstructed to all-atom (AA) representations and refined during molecular dynamics (MD) simulations in explicit solvent. The top-scored protofilament models, selected using symmetry criteria, were used for the assembly of long fibri

SUBMITTER: Kolinski M 

PROVIDER: S-EPMC8621111 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature