title: Exploiting glycogen synthase kinase 3beta flexibility in molecular recognition.
abstract: GSK3beta (glycogen synthase kinase 3beta) is involved in the phosphorylation of various important regulatory proteins. Pharmacological inhibition of this enzyme could yield treatments for a variety of diseases including diabetes and Alzheimer's disease. The understanding of events involved in the molecular recognition of inhibitors by the active site of this enzyme is key in structure-based design strategies. The present study deals with the dynamic nature of GSK3beta and highlights the importance of studying protein plasticity in structure-based drug design, exemplified by our method called ASP (active-site pressurization).
authors.affiliation: Centre for Biomolecular Sciences and School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, U.K.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Mazanetz
authors.forename: Ian M
authors.initials: IM
authors.lastname: Withers
authors.forename: Charles A
authors.initials: CA
authors.lastname: Laughton
authors.forename: Peter M
authors.initials: PM
authors.lastname: Fischer
mesh_terms: D003198:Computer Simulation; D038362:Glycogen Synthase Kinase 3 / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D018583:Pliability; D021281:Quantitative Structure-Activity Relationship
chemical_list: D008024:Ligands; D038362:Glycogen Synthase Kinase 3