Role of conformational sampling in computing mutation-induced changes in protein structure and stability.

ABSTRACT: The prediction of changes in protein stability and structure resulting from single amino acid substitutions is both a fundamental test of macromolecular modeling methodology and an important current problem as high throughput sequencing reveals sequence polymorphisms at an increasing rate. In principle, given the structure of a wild-type protein and a point mutation whose effects are to be predicted, an accurate method should recapitulate both the structural changes and the change in the folding-free energy. Here, we explore the performance of protocols which sample an increasing diversity of conformations. We find that surprisingly similar performances in predicting changes in stability are achieved using protocols that involve very different amounts of conformational sampling, provided t

SUBMITTER: Kellogg EH 

PROVIDER: S-EPMC3760476 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature