Exploiting glycogen synthase kinase 3β flexibility in molecular recognition

GSK3β (glycogen synthase kinase 3β) 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 GSK3β and highlights the importance of studying protein plasticity in structure-based drug design, exemplified by our method called ASP (active-site pressurization).