The role of local backrub motions in evolved and designed mutations.

ABSTRACT: Amino acid substitutions in protein structures often require subtle backbone adjustments that are difficult to model in atomic detail. An improved ability to predict realistic backbone changes in response to engineered mutations would be of great utility for the blossoming field of rational protein design. One model that has recently grown in acceptance is the backrub motion, a low-energy dipeptide rotation with single-peptide counter-rotations, that is coupled to dynamic two-state sidechain rotamer jumps, as evidenced by alternate conformations in very high-resolution crystal structures. It has been speculated that backrubs may facilitate sequence changes equally well as rotamer changes. However, backrub-induced shifts and experimental uncertainty are of similar magnitude for backbone ato

SUBMITTER: Keedy DA 

PROVIDER: S-EPMC3410847 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature