Relationship between protein thermodynamic constraints and variation of evolutionary rates among sites.

ABSTRACT: Evolutionary-rate variation among sites within proteins depends on functional and biophysical properties that constrain protein evolution. It is generally accepted that proteins must be able to fold stably in order to function. However, the relationship between stability constraints and among-sites rate variation is not well understood. Here, we present a biophysical model that links the thermodynamic stability changes due to mutations at sites in proteins ([Formula: see text]) to the rate at which mutations accumulate at those sites over evolutionary time. We find that such a 'stability model' generally performs well, displaying correlations between predicted and empirically observed rates of up to 0.75 for some proteins. We further find that our model has comparable predictive power as d

SUBMITTER: Echave J 

PROVIDER: S-EPMC4391963 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature