Inferring stabilizing mutations from protein phylogenies: application to influenza hemagglutinin.

ABSTRACT: One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (DeltaDeltaG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a furthe

SUBMITTER: Bloom JD 

PROVIDER: S-EPMC2664478 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature