Hybrid approach for including electronic and nuclear quantum effects in molecular dynamics simulations of hydrogen transfer reactions in enzymes
Hybrid approach for including electronic and nuclear quantum effects in molecular dynamics simulations of hydrogen transfer reactions in enzymes
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DOI：
10.1063/1.1356441
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发表时间：
2001-04-15
影响因子：
4.4
通讯作者：
Hammes-Schiffer, S
中科院分区：
文献类型：
--
作者：
Billeter, SR;Webb, SP;Hammes-Schiffer, S
提出了一种模拟酶中质子和氢化物转移反应的混合方法。电子量子效应与经验价键方法相结合。在混合量子/经典分子动力学方法中，氢核被描述为多维振动波函数，考虑了转移氢的核量子效应。得到了作为集体反应坐标函数的自由能分布。导出了将振动绝热核量子效应计入自由能分布的微扰公式。用含量子跃迁的分子动力学(MDQT)表面跃迁方法研究了氢原子振动态之间的非绝热跃迁的动力学效应。MDQT方法与反应通量法相结合来计算传输系数，并研究反应轨迹的实时动力学。这种混合方法包括核量子效应，如零点能量、氢隧穿和激发振动态，以及完整酶和溶剂的动力学。在自由能剖面和动力学轨迹的产生过程中加入了核量子效应，而不是随后作为修正加入。此外，这种方法在分子水平上提供了详细的机理信息，并允许计算速率和动力学同位素效应。还介绍了该方法在肝醇脱氢酶中的初步应用。(C)2001年美国物理研究所。
A hybrid approach for simulating proton and hydride transfer reactions in enzymes is presented. The electronic quantum effects are incorporated with an empirical valence bond approach. The nuclear quantum effects of the transferring hydrogen are included with a mixed quantum/classical molecular dynamics method in which the hydrogen nucleus is described as a multidimensional vibrational wave function. The free energy profiles are obtained as functions of a collective reaction coordinate. A perturbation formula is derived to incorporate the vibrationally adiabatic nuclear quantum effects into the free energy profiles. The dynamical effects are studied with the molecular dynamics with quantum transitions (MDQT) surface hopping method, which incorporates nonadiabatic transitions among the adiabatic hydrogen vibrational states. The MDQT method is combined with a reactive flux approach to calculate the transmission coefficient and to investigate the real-time dynamics of reactive trajectories. This hybrid approach includes nuclear quantum effects such as zero point energy, hydrogen tunneling, and excited vibrational states, as well as the dynamics of the complete enzyme and solvent. The nuclear quantum effects are incorporated during the generation of the free energy profiles and dynamical trajectories rather than subsequently added as corrections. Moreover, this methodology provides detailed mechanistic information at the molecular level and allows the calculation of rates and kinetic isotope effects. An initial application of this approach to the enzyme liver alcohol dehydrogenase is also presented. (C) 2001 American Institute of Physics.