Exploring Routes to Enhance the Calculation of Free Energy Differences via Non-Equilibrium Work SQM/MM Switching Simulations Using Hybrid Charge Intermediates between MM and SQM Levels of Theory or Non-Linear Switching Schemes.
Exploring Routes to Enhance the Calculation of Free Energy Differences via Non-Equilibrium Work SQM/MM Switching Simulations Using Hybrid Charge Intermediates between MM and SQM Levels of Theory or Non-Linear Switching Schemes.
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DOI：
10.3390/molecules28104006
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发表时间：
2023-05-10
期刊：
影响因子：
--
通讯作者：
Boresch S
中科院分区：
文献类型：
--
作者：
Schöller A;Woodcock HL;Boresch S
非平衡工作切换模拟和 Jarzynski 方程是计算两个理论层次之间的自由能差异 的可靠方法，例如感兴趣系统的纯分子力学 (MM) 和量子力学/分子力学 (QM/MM) 描述。尽管具有固有的并行性，但这种方法的计算成本很快就会变得非常高。对于核心区域（要在不同理论层面描述的系统部分）嵌入诸如显式溶剂水等环境中的系统来说尤其如此。我们发现，即使对于相对简单的溶质-水系统，也需要至少 5 ps 的切换长度才能可靠地进行计算。在本研究中，我们研究了两种实现经济实惠协议的方法，重点是保持开关长度远低于 5 ps。插入具有修改的部分电荷的混合电荷中间状态，类似于所需高水平的电荷分布，使得可以通过 2 ps 开关获得可靠的计算。另一方面，使用逐步线性切换路径的尝试并没有带来改进，即所有系统的收敛速度更快。为了理解这些发现，我们分析了溶质的性质作为所使用的部分电荷和与溶质直接接触的水分子数量的函数，并研究了水分子根据溶质电荷分布的变化重新定向所需的时间。
Non-equilibrium work switching simulations and Jarzynski’s equation are a reliable method for computing free energy differences, , between two levels of theory, such as a pure molecular mechanical (MM) and a quantum mechanical/molecular mechanical (QM/MM) description of a system of interest. Despite the inherent parallelism, the computational cost of this approach can quickly become very high. This is particularly true for systems where the core region, the part of the system to be described at different levels of theory, is embedded in an environment such as explicit solvent water. We find that even for relatively simple solute–water systems, switching lengths of at least 5 ps are necessary to compute reliably. In this study, we investigate two approaches towards an affordable protocol, with an emphasis on keeping the switching length well below 5 ps. Inserting a hybrid charge intermediate state with modified partial charges, which resembles the charge distribution of the desired high level, makes it possible to obtain reliable calculations with 2 ps switches. Attempts using step-wise linear switching paths, on the other hand, did not lead to improvement, i.e., a faster convergence for all systems. To understand these findings, we analyzed the solutes’ properties as a function of the partial charges used and the number of water molecules in direct contact with the solute, and studied the time needed for water molecules to reorient themselves upon a change in the solute’s charge distribution.
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影响因子：
4.1
作者：
BENNETT, CH
通讯作者：
BENNETT, CH
影响因子：
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作者：
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影响因子：
1.7
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