Identifying conformational changes of the beta(2) adrenoceptor that enable accurate prediction of ligand/receptor interactions and screening for GPCR modulators.

ABSTRACT: The new beta(2) Adrenoceptor (beta(2)AR) crystal structures provide a high-resolution snapshot of receptor interactions with two particular partial inverse agonists, (-)-carazolol and timolol. However, both experimental and computational studies of GPCR structure are significantly complicated by the existence of multiple conformational states coupled to ligand type and receptor activity. Agonists and antagonists induce or stabilize distinct changes in receptor structure that mediate a range of pharmacological activities. In this work, we (1) established that the existing beta(2)AR crystallographic conformers can be extended to describe ligand/receptor interactions for additional antagonist types, (2) generated agonist-bound receptor conformations, and (3) validated these models for agonist

SUBMITTER: Reynolds KA 

PROVIDER: S-EPMC2667566 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature