Wang Mingliang, Lu Zhenyu, Yang Weitao
Department of Chemistry, Duke University, Durham, North Carolina 27708, USA.
J Chem Phys. 2006 Mar 28;124(12):124516. doi: 10.1063/1.2181145.
Nuclear quantum mechanical effects have been examined for the proton transfer reaction catalyzed by triosephosphate isomerase, with the normal mode centroid path integral molecular dynamics based on the potential energy surface from the recently developed reaction path potential method. In the simulation, the primary and secondary hydrogens and the C and O atoms involving bond forming and bond breaking were treated quantum mechanically, while all other atoms were dealt classical mechanically. The quantum mechanical activation free energy and the primary kinetic isotope effects were examined. Because of the quantum mechanical effects in the proton transfer, the activation free energy was reduced by 2.3 kcal/mol in comparison with the classical one, which accelerates the rate of proton transfer by a factor of 47.5. The primary kinetic isotope effects of kH/kD and kH/kT were estimated to be 4.65 and 9.97, respectively, which are in agreement with the experimental value of 4+/-0.3 and 9. The corresponding Swain-Schadd exponent was predicted to be 3.01, less than the semiclassical limit value of 3.34, indicating that the quantum mechanical effects mainly arise from quantum vibrational motion rather than tunneling. The reaction path potential, in conjunction with the normal mode centroid molecular dynamics, is shown to be an efficient computational tool for investigating the quantum effects on enzymatic reactions involving proton transfer.
利用基于最近开发的反应路径势方法的势能面的正则模质心路径积分分子动力学，研究了磷酸丙糖异构酶催化的质子转移反应中的核量子力学效应。在模拟中，对涉及键形成和键断裂的一级和二级氢以及C和O原子进行量子力学处理，而所有其他原子则采用经典力学处理。研究了量子力学活化自由能和一级动力学同位素效应。由于质子转移中的量子力学效应，活化自由能比经典情况降低了2.3千卡/摩尔，这使得质子转移速率加快了47.5倍。kH/kD和kH/kT的一级动力学同位素效应估计分别为4.65和9.97，与4±0.3和9的实验值一致。预测相应的斯温-沙德指数为3.01，小于半经典极限值3.34，表明量子力学效应主要源于量子振动运动而非隧穿。反应路径势与正则模质心分子动力学相结合，被证明是研究质子转移酶促反应量子效应的有效计算工具。
