Structural insights into conformational stability of wild-type and mutant beta1-adrenergic receptor.

ABSTRACT: Recent experiments to derive a thermally stable mutant of turkey beta-1-adrenergic receptor (beta1AR) have shown that a combination of six single point mutations resulted in a 20 degrees C increase in thermal stability in mutant beta1AR. Here we have used the all-atom force-field energy function to calculate a stability score to detect stabilizing point mutations in G-protein coupled receptors. The calculated stability score shows good correlation with the measured thermal stability for 76 single point mutations and 22 multiple mutants in beta1AR. We have demonstrated that conformational sampling of the receptor for various mutants improve the prediction of thermal stability by 50%. Point mutations Y227A5.58, V230A5.61, and F338M7.48 in the thermally stable mutant m23-beta1AR stabilizes ke

SUBMITTER: Balaraman GS 

PROVIDER: S-EPMC2905111 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature