Faculty of Mathematics and Physics, Institute of Physics, Charles University, Ke Karlovu 5, Prague 2, 121 16, Czech Republic.
J Comput Aided Mol Des. 2013 Apr;27(4):373-88. doi: 10.1007/s10822-013-9652-8. Epub 2013 Apr 26.
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.
使用 CUDA 可编程图形处理单元和 ACEMD 软件包，对诺如病毒 RNA 依赖性 RNA 聚合酶与其天然 CTP 和 2dCTP（均包含连接三磷酸和糖部分的 O5'-C5'-C4'-O4'原子序列）或修饰的 coCTP（C5'-O5'-C4'-O4'）、cocCTP（C5'-O5'-C4'-C4''）复合物进行分子动力学模拟。这使我们能够获得微秒 MD 轨迹，清楚地表明类似的核苷三磷酸可以以惊人的不同方式结合到诺如病毒 RNA 依赖性 RNA 聚合酶的活性部位。这对应于它们不同的作用模式（CTP-底物、2dCTP-贫化底物、coCTP-链终止剂、cocCTP-抑制剂）。此外，还捕获了极其罕见的事件，即 Arg182 反复侵入潜在的促进反应的排列。
