title: Advanced molecular dynamics simulation methods for kinase drug discovery.
abstract: Interest in the application of molecular dynamics (MD) simulations has increased in the field of protein kinase (PK) drug discovery. PKs belong to an important drug target class because they are directly involved in a number of diseases, including cancer. MD methods simulate dynamic biological and chemical events at an atomic level. This information can be combined with other in silico and experimental methods to efficiently target selected receptors. In this review, we present common and advanced methods of MD simulations and we focus on the recent applications of MD-based methodologies that provided significant insights into the elucidation of biological mechanisms involving PKs and into the discovery of novel kinase inhibitors.
authors.affiliation: Institut de Chimie Organique et Analytique (ICOA), UMR CNRS-Université d'Orléans 7311, Université d'Orléans BP 6759, 45067 Orléans Cedex 2, France.
authors.forename: Samia
authors.initials: S
authors.lastname: Aci-Sèche
authors.affiliation: Institut de Chimie Organique et Analytique (ICOA), UMR CNRS-Université d'Orléans 7311, Université d'Orléans BP 6759, 45067 Orléans Cedex 2, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Ziada
authors.affiliation: Institut de Chimie Organique et Analytique (ICOA), UMR CNRS-Université d'Orléans 7311, Université d'Orléans BP 6759, 45067 Orléans Cedex 2, France.
authors.forename: Abdennour
authors.initials: A
authors.lastname: Braka
authors.affiliation: Institut de Chimie Organique et Analytique (ICOA), UMR CNRS-Université d'Orléans 7311, Université d'Orléans BP 6759, 45067 Orléans Cedex 2, France.|Present address: Department of Pathology, Beth Israel Deaconess Medical Center, Boston MA 02215, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Arora
authors.affiliation: Institut de Chimie Organique et Analytique (ICOA), UMR CNRS-Université d'Orléans 7311, Université d'Orléans BP 6759, 45067 Orléans Cedex 2, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Bonnet
mesh_terms: D015195:Drug Design; D055808:Drug Discovery; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D058990:Molecular Targeted Therapy; D011485:Protein Binding; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; D011494:Protein Kinases
keywords: conformational sampling; drug discovery; molecular dynamics simulation; protein kinase; protein–ligand association process; structure–kinetics relationship