Use of Nonequilibrium Work Methods to Compute Free Energy Differences Between Molecular Mechanical and Quantum Mechanical Representations of Molecular Systems
Use of Nonequilibrium Work Methods to Compute Free Energy Differences Between Molecular Mechanical and Quantum Mechanical Representations of Molecular Systems
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DOI：
10.1021/acs.jpclett.5b02164
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发表时间：
2015-12-03
影响因子：
5.7
通讯作者：
Boresch, Stefan
中科院分区：
文献类型：
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作者：
Hudson, Phillip S.;Woodcock, H. Lee;Boresch, Stefan
使用量子力学（QM）Harniltonian进行自由能模拟（FES）仍然是一个有吸引力的，尽管难以捉摸的目标。在这一领域的新的努力集中在使用“间接”热力学循环连接“低级别”的模拟结果，以“高级别”的自由能。计算分子力学（MM）和QM（Δ A（MM -> QM））之间的收敛自由能结果的主要障碍，如我们和其他人最近所证明的，是所谓的“刚性”自由度的差异（例如，键拉伸）。在这里，我们证明，这个问题可以有效地规避使用非平衡工作（新）技术，即，Jarzynski和Crooks的方程式。计算Delta A（NEW）（MM -> QM）的初步应用，对于封闭的氨基酸丙氨酸和丝氨酸以及生成丁烷的电位间接QM/MM FES方法，显示出比传统FES方法显著的改进。
Carrying out free energy simulations (FES) using quantum mechanical (QM) Harniltonians remains an attractive, albeit elusive goal. Renewed efforts in this area have focused on using "indirect" thermodynamic cycles to connect "low level" simulation results to "high level" free energies. The main obstacle to computing converged free energy results between molecular mechanical (MM) and QM (Delta A(MM -> QM)), as recently demonstrated by us and others, is differences in the so-called "stiff" degrees of freedom (e.g., bond stretching) between the respective energy surfaces. Herein, we demonstrate that this problem can be efficiently circumvented using nonequilibrium work (NEW) techniques, i.e., Jarzynski's and Crooks' equations. Initial applications of computing Delta A(NEW)(MM -> QM), for blocked amino acids alanine and serine as well as to generate butane's potentials indirect QM/MM FES method, showed marked improvement over traditional FES approaches.