The role of negative selection in protein evolution revealed through the energetics of the native state ensemble.

ABSTRACT: Knowing the determinants of conformational specificity is essential for understanding protein structure, stability, and fold evolution. To address this issue, a novel statistical measure of energetic compatibility between sequence and structure was developed using an experimentally validated model of the energetics of the native state ensemble. This approach successfully matched sequences from a diverse subset of the human proteome to their respective folds. Unexpectedly, significant energetic compatibility between ostensibly unrelated sequences and structures was also observed. Interrogation of these matches revealed a general framework for understanding the origins of conformational specificity within a proteome: specificity is a complex function of both the ability of a sequence to adop

SUBMITTER: Hoffmann J 

PROVIDER: S-EPMC4811355 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature