title: Substrate recognition by norovirus polymerase: microsecond molecular dynamics study.
abstract: Molecular dynamics simulations of complexes between Norwalk virus RNA dependent RNA polymerase and its natural CTP and 2dCTP (both containing the O5'-C5'-C4'-O4' sequence of atoms bridging the triphosphate and sugar moiety) or modified coCTP (C5'-O5'-C4'-O4'), cocCTP (C5'-O5'-C4'-C4'') substrates were produced by means of CUDA programmable graphical processing units and the ACEMD software package. It enabled us to gain microsecond MD trajectories clearly showing that similar nucleoside triphosphates can bind surprisingly differently into the active site of the Norwalk virus RNA dependent RNA polymerase. It corresponds to their different modes of action (CTP-substrate, 2dCTP-poor substrate, coCTP-chain terminator, cocCTP-inhibitor). Moreover, extremely rare events-as repetitive pervasion of Arg182 into a potentially reaction promoting arrangement-were captured.
authors.affiliation: Faculty of Mathematics and Physics, Institute of Physics, Charles University, Ke Karlovu 5, Prague 2, 121 16, Czech Republic.
authors.forename: Kamil
authors.initials: K
authors.lastname: Maláč
authors.forename: Ivan
authors.initials: I
authors.lastname: Barvík
mesh_terms: D017250:Caliciviridae Infections / Q000821:virology; D003570:Cytidine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism*; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D029322:Norovirus / Q000201:enzymology* / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D003570:Cytidine Triphosphate; D012324:RNA-Dependent RNA Polymerase