Accelerated computation of free energy profile at ab initio quantum mechanical/molecular mechanical accuracy via a semi-empirical reference potential. II. Recalibrating semi-empirical parameters with force matching
Accelerated computation of free energy profile at ab initio quantum mechanical/molecular mechanical accuracy via a semi-empirical reference potential. II. Recalibrating semi-empirical parameters with force matching
复制标题
通过半经验参考势以从头开始的量子力学/分子力学精度加速计算自由能剖面。
DOI：
10.1039/c9cp02593f
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发表时间：
2019-10-07
影响因子：
3.3
通讯作者：
Shao, Yihan
中科院分区：
文献类型：
--
作者：
Pan, Xiaoliang;Li, Pengfei;Shao, Yihan
提出了一种高效、准确的参考势模拟方案，用于生成溶剂或大分子环境中化学反应的从头算量子力学/分子力学（AI-QM/MM）质量自由能分布。该方案包括三个阶段：（a）使用力匹配重新校准所研究的特定反应的半经验量子力学（SE-QM）哈密顿量;（B）使用重新校准的SE-QM哈密顿量（与分子机械力场结合）作为参考电势以沿着反应途径驱动伞形取样;以及（c）计算来自所述采样的所收集构型的AI-QM/MM能量值，并执行加权热力学扰动以获得AI-QM/MM校正的反应自由能分布。对于三个模型反应，（同一性S（N）2反应、Menshutkin反应和甘氨酸质子转移反应）和一种酶反应（分支酸盐中的克莱森排列），我们使用重新校准的PM 3 SE-QM哈密顿量进行的模拟，在理论的B3 LYP/6- 31 G * 水平上很好地再现了QM/MM自由能分布，所有这些都在1 kcal mol（-1）以内。计算机时间减少了20到45倍。
An efficient and accurate reference potential simulation protocol is proposed for producing ab initio quantum mechanical/molecular mechanical (AI-QM/MM) quality free energy profiles for chemical reactions in a solvent or macromolecular environment. This protocol involves three stages: (a) using force matching to recalibrate a semi-empirical quantum mechanical (SE-QM) Hamiltonian for the specific reaction under study; (b) employing the recalibrated SE-QM Hamiltonian (in combination with molecular mechanical force fields) as the reference potential to drive umbrella samplings along the reaction pathway; and (c) computing AI-QM/MM energy values for collected configurations from the sampling and performing weighted thermodynamic perturbation to acquire an AI-QM/MM corrected reaction free energy profile. For three model reactions (identity S(N)2 reaction, Menshutkin reaction, and glycine proton transfer reaction) in aqueous solution and one enzyme reaction (Claisen arrangement in chorismate mutase), our simulations using recalibrated PM3 SE-QM Hamiltonians well reproduced QM/MM free energy profiles at the B3LYP/6-31G* level of theory all within 1 kcal mol(-1) with a 20 to 45 fold reduction in the computer time.