Explicit-solvent molecular dynamics simulation at constant pH:: Methodology and application to small amines
Explicit-solvent molecular dynamics simulation at constant pH:: Methodology and application to small amines
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DOI：
10.1063/1.1370959
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发表时间：
2001-06-08
影响因子：
4.4
通讯作者：
Hünenberger, PH
中科院分区：
文献类型：
--
作者：
Börjesson, U;Hünenberger, PH
开发了一种用于在恒定pH下进行经典显式溶剂分子动力学（MD）模拟的方法，其中允许模拟化合物中每个可电离（可滴定）基团的质子化状态随时间波动，这取决于瞬时系统配置和施加的pH。在该方法中，每个可电离基团被视为混合状态，即，基团的相互作用函数参数是质子化状态和去质子化状态的相互作用函数参数的线性组合。自由质子没有明确处理。相反，每个基团的去质子化程度通过与“质子浴”的弱耦合而向其平衡值放松。“该方法依赖于预先校准的经验函数，一个用于模拟化合物中存在的每种类型的可电离基团，这是通过单官能模型化合物的多次MD模拟获得的。在这项研究中，该方法进行了详细描述，并说明了一系列恒定pH值的MD模拟小单官能胺的应用。特别是，我们调查的影响，在弱耦合方案中使用的弛豫时间，选择适当的模型化合物所需的经验函数的校准，并与模拟箱的小尺寸的有限尺寸效应的校正。(C)2001年美国物理学会。
A method is developed for performing classical explicit-solvent molecular dynamics (MD) simulations at constant pH, where the protonation state of each ionizable (titratable) group in a simulated compound is allowed to fluctuate in time, depending on the instantaneous system configuration and the imposed pH. In this method, each ionizable group is treated as a mixed state, i.e., the interaction-function parameters for the group are a linear combination of those of the protonated state and those of the deprotonated state. Free protons are not handled explicitly. Instead, the extent of deprotonation of each group is relaxed towards its equilibrium value by weak coupling to a "proton bath." The method relies on precalibrated empirical functions, one for each type of ionizable group present in the simulated compound, which are obtained through multiple MD simulations of monofunctional model compounds. In this study, the method is described in detail and its application illustrated by a series of constant-pH MD simulations of small monofunctional amines. In particular, we investigate the influence of the relaxation time used in the weak-coupling scheme, the choice of appropriate model compounds for the calibration of the required empirical functions, and corrections for finite-size effects linked with the small size of the simulation box. (C) 2001 American Institute of Physics.