Design principles for high-pressure force fields: Aqueous TMAO solutions from ambient to kilobar pressures
Design principles for high-pressure force fields: Aqueous TMAO solutions from ambient to kilobar pressures
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DOI：
10.1063/1.4944991
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发表时间：
2016-04-14
影响因子：
4.4
通讯作者：
Kast, Stefan M.
中科院分区：
文献类型：
--
作者：
Hoelzl, Christoph;Kibies, Patrick;Kast, Stefan M.
精确的力场是成功进行复杂生物分子过程分子动力学模拟的主要支柱之一。它们已经针对环境条件进行了优化，而高压模拟在压力扰动研究中变得越来越重要，使用压力作为独立的热力学变量。在这里，我们探索非极化力场的设计，以在千巴压力范围内很好地工作，同时避免完全的重新参数化。我们的关键是首先通过结合积分方程式方法来计算溶质的压力诱导的电子和结构响应，该方法将对溶剂结构的压力效应与嵌入的团簇参考相互作用中心模型(EC-RISM)框架内的溶质的量子化学处理相结合。其次，通过在已建立的力场的选定参数中引入压力依赖关系来考虑溶质对压缩的响应。在我们的原理证明研究中，完整的机械应用于水中的N，N，N-三甲胺-N-氧化物(TMAO)，TMAO是一种有效的渗透分子，可以中和压力变性。ECRISM理论很好地描述了TMAO(Aq)压缩到10kbar时的电荷再分布，然后通过压力相关的部分电荷体现在力场分子动力学中。通过与实验数据和从头算分子动力学数据的比较，评估了高压力场的性能。除了在极端热力学条件下设计不可极化力场的广泛用途外，在构造和验证可极化力场时，强烈建议对溶液的压力响应进行良好的描述。(C)2016 AIP出版有限责任公司。
Accurate force fields are one of the major pillars on which successful molecular dynamics simulations of complex biomolecular processes rest. They have been optimized for ambient conditions, whereas high-pressure simulations become increasingly important in pressure perturbation studies, using pressure as an independent thermodynamic variable. Here, we explore the design of non-polarizable force fields tailored to work well in the realm of kilobar pressures - while avoiding complete reparameterization. Our key is to first compute the pressure-induced electronic and structural response of a solute by combining an integral equation approach to include pressure effects on solvent structure with a quantum-chemical treatment of the solute within the embedded cluster reference interaction site model (EC-RISM) framework. Next, the solute's response to compression is taken into account by introducing pressure-dependence into selected parameters of a well-established force field. In our proof-of-principle study, the full machinery is applied to N,N,N-trimethylamine-N-oxide (TMAO) in water being a potent osmolyte that counteracts pressure denaturation. EC-RISM theory is shown to describe well the charge redistribution upon compression of TMAO(aq) to 10 kbar, which is then embodied in force field molecular dynamics by pressure-dependent partial charges. The performance of the high pressure force field is assessed by comparing to experimental and ab initio molecular dynamics data. Beyond its broad usefulness for designing non-polarizable force fields for extreme thermodynamic conditions, a good description of the pressure-response of solutions is highly recommended when constructing and validating polarizable force fields. (C) 2016 AIP Publishing LLC.