Essential Dynamics Ensemble Docking for Structure-Based GPCR Drug Discovery.

ABSTRACT: The lack of biologically relevant protein structures can hinder rational design of small molecules to target G protein-coupled receptors (GPCRs). While ensemble docking using multiple models of the protein target is a promising technique for structure-based drug discovery, model clustering and selection still need further investigations to achieve both high accuracy and efficiency. In this work, we have developed an original ensemble docking approach, which identifies the most relevant conformations based on the essential dynamics of the protein pocket. This approach is applied to the study of small-molecule antagonists for the PAC1 receptor, a class B GPCR and a regulator of stress. As few as four representative PAC1 models are selected from simulations of a homology model and then used t

SUBMITTER: McKay K 

PROVIDER: S-EPMC9277106 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature