Theory of Sequence Effects in Amyloid Aggregation.

ABSTRACT: We present a simple model for the effect of amino acid sequences on amyloid fibril formation. Using the HP model we find the binding lifetimes of four simple sequences by solving the first passage time for the intermolecular H-bond reaction coordinate. We find that sequences with identical binding energies have widely varying binding times depending on where the aggregation prone amino acids are located in the sequence. In general, longer binding times occur when the aggregation prone amino acids are clustered in a single "hot spot". Similarly, binding times are shortened by clustering weakly bound residues. Both of these effects are explained by an increase in the multiplicity of unbinding trajectories that comes from adding weak binding residues. Our model predicts a transition from orde

SUBMITTER: Huang C 

PROVIDER: S-EPMC6082164 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature