title: Cyclin-dependent kinases: bridging their structure and function through computations.
abstract: Cyclin-dependent kinases (CDKs) are one of the most promising target families for drug discovery for several diseases, such as cancer and neurodegenerative disorders. Over the years, structural insights on CDKs have demonstrated high protein plasticity, with several cases where two or more structures of the same protein adopt different conformations. This has generated a great deal of interest in understanding the relationship between CDK structure and function. Here, we highlight how computer simulations have recently contributed in characterizing some key rare and transient events in CDKs, such as the reaction transition state and activation loop movement. Although not yet fully defined, we can now portray the enzymatic mechanism and plasticity of CDKs at high spatial and temporal resolution. These theoretical studies bridge with experiments and highlight structural determinants that could help in designing specific CDK inhibitors.
authors: Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy.
authors: Marco
authors: M
authors: De Vivo
authors: Giovanni
authors: G
authors: Bottegoni
authors: Anna
authors: A
authors: Berteotti
authors: Maurizio
authors: M
authors: Recanatini
authors: Francesco Luigi
authors: FL
authors: Gervasio
authors: Andrea
authors: A
authors: Cavalli
mesh_terms: D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D005786:Gene Expression Regulation; D008962:Models, Theoretical; D056004:Molecular Dynamics Simulation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D047428:Protein Kinase Inhibitors; D018844:Cyclin-Dependent Kinases