title: Enzyme millisecond conformational dynamics do not catalyze the chemical step.
abstract: The idea that enzymes catalyze reactions by dynamical coupling between the conformational motions and the chemical coordinates has recently attracted major experimental and theoretical interest. However, experimental studies have not directly established that the conformational motions transfer energy to the chemical coordinate, and simulating enzyme catalysis on the relevant timescales has been impractical. Here, we introduce a renormalization approach that transforms the energetics and dynamics of the enzyme to an equivalent low-dimensional system, and allows us to simulate the dynamical coupling on a ms timescale. The simulations establish, by means of several independent approaches, that the conformational dynamics is not remembered during the chemical step and does not contribute significantly to catalysis. Nevertheless, the precise nature of this coupling is a question of great importance.
authors.affiliation: Department of Chemistry SGM 418, University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089, USA.
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Pisliakov
authors.forename: Jie
authors.initials: J
authors.lastname: Cao
authors.forename: Shina C L
authors.initials: SC
authors.lastname: Kamerlin
authors.forename: Arieh
authors.initials: A
authors.lastname: Warshel
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000737:chemistry / Q000378:metabolism; D002151:Calorimetry; D002384:Catalysis; D003198:Computer Simulation; D004735:Energy Transfer; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D011485:Protein Binding; D011487:Protein Conformation; D013816:Thermodynamics
chemical_list: D004798:Enzymes; D008024:Ligands; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D000263:Adenylate Kinase