Department of Chemistry and Biochemistry, University of Montana, Missoula, MT 59812, USA.
Phys Chem Chem Phys. 2021 May 5;23(17):10524-10535. doi: 10.1039/d1cp00688f.
In this study we report on the accurate computation of the biomolecular partial specific volume (PSV) from explicit-solvent molecular dynamics (MD) simulations. The case of DNA is considered, and the predictions from two state-of-the-art biomolecular force fields, the CHARMM36 additive (C36) and Drude polarizable models, are presented. Unlike most of the existing approaches to assess the biomolecular PSV, our proposed method bypasses the need for the arbitrarily defined volume partitioning scheme into the intrinsic solute and solvent contributions. At the same time, to assess the density of the hydration layer water, we combine our simulation analysis approach with some of the existing fixed-size methods to determine the solute's intrinsic volume, and also propose our own approach to compute all required quantities exclusively from MD simulations. Our findings provide useful insights into the properties of the hydration layer, specifically its size and density, parameters of great importance to the variety of techniques used to model hydrodynamic and structural properties of biological molecules. The computed PSV values are found to be in close agreement with the values obtained from analytical ultracentrifugation (AUC) experiments performed on canonical B-form duplex DNAs and single-stranded DNAs forming G-quadruplex structures. Since the biomolecular PSV represents an important quantitative measure of solute-solvent interactions, near quantitative agreement with AUC measurements is indicative of the quality of the all-atom models used in the MD simulations, particularly the reliability of the CHARMM force-field parameters for nucleic acids, water, mobile ions, and interactions among these entities.
在本研究中，我们报告了从显式溶剂分子动力学（MD）模拟准确计算生物分子偏比容（PSV）的方法。考虑了 DNA 的情况，并提出了两种最先进的生物分子力场，即 CHARMM36 加性（C36）和 Drude 极化模型的预测。与评估生物分子 PSV 的大多数现有方法不同，我们提出的方法避免了将体积任意划分为固有溶质和溶剂贡献的需要。同时，为了评估水合层水的密度，我们将我们的模拟分析方法与一些现有的固定尺寸方法相结合，以确定溶质的固有体积，还提出了自己的方法，仅从 MD 模拟中计算所有必需的量。我们的发现为水合层的性质，特别是其大小和密度，提供了有用的见解，这些参数对用于模拟生物分子流体动力学和结构性质的各种技术非常重要。计算得到的 PSV 值与在典型 B 型双链 DNA 和形成 G-四链体结构的单链 DNA 上进行的分析超速离心（AUC）实验获得的值非常吻合。由于生物分子 PSV 是溶质-溶剂相互作用的重要定量度量，因此与 AUC 测量值的近乎定量吻合表明 MD 模拟中使用的全原子模型的质量，特别是核酸、水、移动离子以及这些实体之间相互作用的 CHARMM 力场参数的可靠性。
