Rapid Computational Prediction of Thermostabilizing Mutations for G Protein-Coupled Receptors.

ABSTRACT: G protein-coupled receptors (GPCRs) are highly dynamic and often denature when extracted in detergents. Deriving thermostable mutants has been a successful strategy to stabilize GPCRs in detergents, but this process is experimentally tedious. We have developed a computational method to predict the position of the thermostabilizing mutations for a given GPCR sequence. We have validated the method against experimentally measured thermostability data for single mutants of the β₁-adrenergic receptor (β₁AR), adenosine A_2A receptor (A_2AR) and neurotensin receptor 1 (NTSR1). To make these predictions we started from homology models of these receptors of varying accuracies and generated an ensemble of conformations by sampling the rigid body degrees of f

SUBMITTER: Bhattacharya S 

PROVIDER: S-EPMC4230369 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature