Improved prediction of site-rates from structure with averaging across homologs.

ABSTRACT: Variation in mutation rates at sites in proteins can largely be understood by the constraint that proteins must fold into stable structures. Models that calculate site-specific rates based on protein structure and a thermodynamic stability model have shown a significant but modest ability to predict empirical site-specific rates calculated from sequence. Models that use detailed atomistic models of protein energetics do not outperform simpler approaches using packing density. We demonstrate that a fundamental reason for this is that empirical site-specific rates are the result of the average effect of many different microenvironments in a phylogeny. By analyzing the results of evolutionary dynamics simulations, we show how averaging site-specific rates across many extant protein structures

SUBMITTER: Norn C 

PROVIDER: S-EPMC11196898 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature