The ion atmosphere surrounding highly charged biomolecules, such as nucleic acids, is crucial for their dynamics, structure, and interactions. Here, we develop an approach for the explicit treatment of ions within an implicit solvent framework suitable for atomistic simulations of biomolecules. The proposed implicit solvent/explicit ions model, GBION, is based on a modified generalized Born (GB) model; it includes separate, modified GB terms for solute–ion and ion–ion interactions. The model is implemented in the AMBER package (version 24), and its performance is thoroughly investigated in atomistic molecular dynamics (MD) simulations of double-stranded DNA on a microsecond time scale. The aggregate characteristics of monovalent (Na⁺ and K⁺) and trivalent (Cobalt Hexammine, CoHex³⁺) counterion distributions around double-stranded DNA predicted by the model are in reasonable agreement with the experiment (where available), all-atom explicit water MD simulations, and the expectation from the Manning condensation theory. The radial distributions of monovalent cations around DNA are reasonably close to the ones obtained using the explicit water model: expressed in units of energy, the maximum deviations of local ion concentrations from the explicit solvent reference are within 1 k_BT, comparable to the corresponding deviations expected between different established explicit water models. The proposed GBION model is able to simulate DNA fragments in a large volume of solvent with explicit ions with little additional computational overhead compared with the fully implicit GB treatment of ions. Ions simulated using the developed model explore conformational space at least 2 orders of magnitude faster than in the explicit solvent. These advantages allowed us to observe and explore an unexpected “stacking” mode of DNA condensation in the presence of trivalent counterions (CoHex³⁺) that was revealed by recent experiments.

中文翻译：

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分子动力学中具有显式离子的隐式溶剂广义 Born 模型：在 DNA 中的应用


高电荷生物分子（如核酸）周围的离子气氛对其动力学、结构和相互作用至关重要。在这里，我们开发了一种在隐式溶剂框架内显式处理离子的方法，适用于生物分子的原子模拟。提出的隐式溶剂/显式离子模型 GBION 基于改进的广义 Born （GB） 模型;它包括溶质-离子和离子-离子相互作用的单独修改的 GB 项。该模型在 AMBER 包（版本 24）中实现，并在微秒时间尺度上对双链 DNA 的原子分子动力学 （MD） 模拟进行了彻底的研究。模型预测的双链 DNA 周围单价（Na⁺ 和 K⁺）和三价（钴六胺、CoHex³⁺）反离子分布的聚集特性与实验（如果可用）、全原子显式水 MD 模拟和曼宁缩合理论的预期合理一致。DNA 周围一价阳离子的径向分布与使用显式水模型获得的径向分布相当接近：以能量单位表示，局部离子浓度与显式溶剂参考的最大偏差在 1 k_BT 以内，与不同已建立的显式水模型之间的预期相应偏差相当。与离子的完全隐式 GB 处理相比，所提出的 GBION 模型能够模拟具有显式离子的大量溶剂中的 DNA 片段，而额外的计算开销很小。 使用开发的模型模拟的离子探索构象空间的速度比显式溶剂快至少 2 个数量级。这些优势使我们能够观察和探索在三价对离子 （CoHex³⁺） 存在下 DNA 缩合的意想不到的“堆积”模式，最近的实验揭示了这种模式。