Setny Piotr
Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097 Warsaw, Poland.
J Phys Chem B. 2015 May 14;119(19):5970-8. doi: 10.1021/acs.jpcb.5b01982. Epub 2015 Apr 30.
In our previous work, we introduced a solvation model based on discrete solvent representation and demonstrated its ability to estimate hydration free energies for neutral solutes. Here, we present modifications extending the applicability of the model to charged solutes. They include improvements in the representation of the first hydration shell and systematic treatment of long-range interactions. While sharing computational efficiency of implicit solvent models, our approach avoids some of their important limitations, both in the context of electrostatic and nonpolar hydration effects: it naturally captures hydration asymmetry of opposite charges, it relies on solute description by standard all atom force fields instead of utilizing specialized sets of atomic parameters, it predicts solvent distribution in space without the need to geometrically define solvent accessible surface. By combining discrete solvent representation in vicinity of a solute with continuum description of long-range interactions, the model addresses two distinct aspects of biomolecular hydration: complex, short-range effects arising due to molecular nature of aqueous solvent, and bulk contributions. We demonstrate that the model provides good agreement with experimental results for an extensive set of roughly 700 diverse compounds, including neutral and charged solutes with hydration free energies ranging from +3.4 to -536 kcal/mol.
在我们之前的工作中，我们引入了一种基于离散溶剂表示的溶剂化模型，并证明了其估算中性溶质水合自由能的能力。在此，我们提出了一些改进措施，将该模型的适用性扩展到带电溶质。这些改进包括对第一水合层表示的优化以及对长程相互作用的系统处理。在共享隐式溶剂模型计算效率的同时，我们的方法避免了它们在静电和非极性水合效应方面的一些重要局限性：它自然地捕捉了相反电荷的水合不对称性，它依赖于标准全原子力场对溶质的描述，而不是使用专门的原子参数集，它无需几何定义溶剂可及表面就能预测空间中的溶剂分布。通过将溶质附近的离散溶剂表示与长程相互作用的连续介质描述相结合，该模型解决了生物分子水合的两个不同方面：由于水性溶剂的分子性质产生的复杂短程效应和整体贡献。我们证明，对于大约700种不同化合物的广泛集合，包括水合自由能范围从+3.4到-536 kcal/mol的中性和带电溶质，该模型与实验结果具有良好的一致性。
