title: Conformational transition paths harbor structures useful for aiding drug discovery and understanding enzymatic mechanisms in protein kinases.
abstract: This short article examines the usefulness of fast simulations of conformational transition paths in elucidating enzymatic mechanisms and guiding drug discovery for protein kinases. It applies the transition path method in the MOIL software package to simulate the paths of conformational transitions between six pairs of structures from the Protein Data Bank. The structures along the transition paths were found to resemble experimental structures that mimic transient structures believed to form during enzymatic catalysis or conformational transitions, or structures that have drug candidates bound. These findings suggest that such simulations could provide quick initial insights into the enzymatic mechanisms or pathways of conformational transitions of proteins kinases, or could provide structures useful for aiding structure-based drug design.
authors.affiliation: Department of Chemistry and Biochemistry and Center for Nanoscience, University of Missouri-Saint Louis, Saint Louis, Missouri, 63121.
authors.forename: Chung F
authors.initials: CF
authors.lastname: Wong
mesh_terms: D055162:Biocatalysis; D055808:Drug Discovery; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D012984:Software
chemical_list: D047428:Protein Kinase Inhibitors; D011494:Protein Kinases
keywords: catalytic mechanisms of protein kinases; conformational transition paths; protein kinases; structures for ensemble docking