The Dynamic Process of Drug–GPCR Binding at Either Orthosteric or Allosteric Sites Evaluated by Metadynamics [chapter]

Sebastian Schneider, Davide Provasi, Marta Filizola
2015 Msphere  
Major advances in G Protein-Coupled Receptor (GPCR) structural biology over the past few years have yielded a significant number of high-resolution crystal structures for several different receptor subtypes. This dramatic increase in GPCR structural information has underscored the use of automated docking algorithms for the discovery of novel ligands that can eventually be developed into improved therapeutics. However, these algorithms are often unable to discriminate between different, yet
more » ... getically similar, poses because of their relatively simple scoring functions. Here, we describe a metadynamics-based approach to study the dynamic process of ligand binding to/unbinding from GPCRs with a higher level of accuracy and yet satisfying efficiency.
doi:10.1007/978-1-4939-2914-6_18 pmid:26260607 pmcid:PMC4703114 fatcat:riyvg65ucvd5djgsylmakbi23a