title: Binding Kinetics in Drug Discovery.
abstract: Over the last years, researchers have increasingly become interested in measuring and understanding drugs' binding kinetics, namely the time in which drug and its target associate and dissociate. Historically, drug discovery programs focused on the optimization of target affinity as a proxy of in-vivo efficacy. However, often the efficacy of a ligand is not appropriately described by the in-vitro measured drug-receptor affinity, but rather depends on the lifetime of the in-vivo drug-receptor interaction. In this review we review recent works that highlight the importance of binding kinetics, molecular determinants for rational optimization and the recent emergence of computational methods as powerful tools in measuring and understanding binding kinetics.
authors: Computational Biophysics Laboratory (GRIB-IMIM), Universitat Pompeu Fabra,Barcelona Biomedical Research Park (PRBB), C Dr Aiguader 88, 08003, Barcelona, Spain.|Acellera, Barcelona Biomedical Research Park (PRBB), C Dr Aiguader 88, 08003, Barcelona, Spain.
authors: Noelia
authors: N
authors: Ferruz
authors: Computational Biophysics Laboratory (GRIB-IMIM), Universitat Pompeu Fabra,Barcelona Biomedical Research Park (PRBB), C Dr Aiguader 88, 08003, Barcelona, Spain. gianni.defabritiis@upf.edu.|Institució Catalana de Recerca i Estudis Avançats, Passeig Lluis Companys 23, 08010, Barcelona, Spain. gianni.defabritiis@upf.edu.
authors: Gianni
authors: G
authors: De Fabritiis
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007700:Kinetics; D013816:Thermodynamics
keywords: adaptive sampling; binding kinetics; drug discovery; molecular dynamics