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首页> 外文期刊>Chemistry: A European journal >Do dynamic effects play a significant role in enzymatic catalysis? A theoretical analysis of formate dehydrogenase
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Do dynamic effects play a significant role in enzymatic catalysis? A theoretical analysis of formate dehydrogenase

机译：动态效应在酶催化中是否起重要作用？甲酸脱氢酶的理论分析

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A theoretical study of the protein dynamic effects on the hydride transfer between the formate anion and nicotinamide adenine dinucleotide (NAD+), catalyzed by formate dehy- drogenase (FDH), is presented in this paper. The analysis of free downhill molecular dynamic trajectories, performed in the enzyme and compared with the reaction in aqueous solution, has allowed the study of the dynamic coupling between the reacting fragments and the protein or the solvent water molecules, as well as an estimation of the dynamic effect contribution to the catalytic effect from calculation of the transmission coefficient in the enzyme and in solution. The obtained transmission coefficients for the enzyme and in solution were 0.46 ± 0.04 and 0.20 ± 0.03, respectively. These values represent a contribution to catalysis of 0.5 kcalmol~(-1), which, although small, is not negligible keeping in mind the low efficiency of FDH. The analysis of the reactive trajectories also reveals how the relative movements of some amino acids, mainly His332 and Arg284, precede and promote the chemical reaction. In spite of these movements, the time-dependent evolution of the electric field created by the enzyme on the key atoms of the reaction reveals a permanent field, which reduces the work required to reach the transition state, with a concomitant polarization of the cofactor. Finally, application of Grote-Hynes theory has allowed the identification of the modes responsible for the substrate-environment coupling, showing how some protein motions take place simultaneously with the reaction. Thus, the equilibrium approach would provide, in this case, an overestimation of the catalyzed rate constant.
机译：本文提出了蛋白质动力学对甲酸脱氢酶（FDH）催化的甲酸阴离子与烟酰胺腺嘌呤二核苷酸（NAD +）之间氢化物转移的动力学研究。通过在酶中进行的自由下坡分子动力学轨迹的分析以及与水溶液中的反应进行比较，可以研究反​​应片段与蛋白质或溶剂水分子之间的动力学偶联，并估算通过计算酶和溶液中的传递系数，动态效应对催化作用的贡献。所获得的酶和溶液中的传递系数分别为0.46±0.04和0.20±0.03。这些值代表0.5 kcalmol〜（-1）的催化作用，尽管该值很小，但要记住FDH的效率很低。反应轨迹的分析还揭示了某些氨基酸（主要是His332和Arg284）的相对运动是如何先于并促进化学反应的。尽管有这些运动，但是由酶在反应关键原子上产生的电场随时间的变化揭示了一个永久电场，该永久电场减少了达到过渡态所需的功，同时伴随着辅助因子的极化。最终，Grote-Hynes理论的应用已经允许鉴定负责底物-环境偶联的模式，显示出一些蛋白质运动是如何与反应同时发生的。因此，在这种情况下，平衡方法将提供对催化速率常数的高估。

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