Sequence entropy of folding and the absolute rate of amino acid substitutions.

ABSTRACT: Adequate representations of protein evolution should consider how the acceptance of mutations depends on the sequence context in which they arise. However, epistatic interactions among sites in a protein result in hererogeneities in the substitution rate, both temporal and spatial, that are beyond the capabilities of current models. Here we use parallels between amino acid substitutions and chemical reaction kinetics to develop an improved theory of protein evolution. We constructed a mechanistic framework for modelling amino acid substitution rates that uses the formalisms of statistical mechanics, with principles of population genetics underlying the analysis. Theoretical analyses and computer simulations of proteins under purifying selection for thermodynamic stability show that substit

SUBMITTER: Goldstein RA 

PROVIDER: S-EPMC5701738 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature