title: Modeling the effect of pathogenic mutations on the conformational landscape of protein kinases.
abstract: Most proteins assume different conformations to perform their cellular functions. This conformational dynamics is physiologically regulated by binding events and post-translational modifications, but can also be affected by pathogenic mutations. Atomistic molecular dynamics simulations complemented by enhanced sampling approaches are increasingly used to probe the effect of mutations on the conformational dynamics and on the underlying conformational free energy landscape of proteins. In this short review we discuss recent successful examples of simulations used to understand the molecular mechanism underlying the deregulation of physiological conformational dynamics due to non-synonymous single point mutations. Our examples are mostly drawn from the protein kinase family.
authors.affiliation: Department of Chemistry, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Saladino
authors.affiliation: Department of Chemistry, University College London, London WC1E 6BT, United Kingdom; Research Institute of Structural and Molecular Biology, University College London, London WC1E 6BT, United Kingdom. Electronic address: f.l.gervasio@ucl.ac.uk.
authors.forename: Francesco Luigi
authors.initials: FL
authors.lastname: Gervasio
mesh_terms: D004351:Drug Resistance / Q000235:genetics; D056004:Molecular Dynamics Simulation; D009154:Mutation; D009857:Oncogenes; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics
chemical_list: D011494:Protein Kinases