Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, United States of America.
Vancouver Prostate Centre, Vancouver, British Columbia, Canada.
PLoS One. 2019 Jul 10;14(7):e0219473. doi: 10.1371/journal.pone.0219473. eCollection 2019.
Computed, high-resolution, spatial distributions of solvation energy and entropy can provide detailed information about the role of water in molecular recognition. While grid inhomogeneous solvation theory (GIST) provides rigorous, detailed thermodynamic information from explicit solvent molecular dynamics simulations, recent developments in the 3D reference interaction site model (3D-RISM) theory allow many of the same quantities to be calculated in a fraction of the time. However, 3D-RISM produces atomic-site, rather than molecular, density distributions, which are difficult to extract physical meaning from. To overcome this difficulty, we introduce a method to reconstruct molecular density distributions from atomic-site density distributions. Furthermore, we assess the quality of the resulting solvation thermodynamics density distributions by analyzing the binding site of coagulation Factor Xa with both GIST and 3D-RISM. We find good qualitative agreement between the methods for oxygen and hydrogen densities as well as direct solute-solvent energetic interactions. However, 3D-RISM predicts lower energetic and entropic penalties for moving water from the bulk to the binding site.
计算得到的、高分辨率的溶剂化能和熵的空间分布，可以为水在分子识别中的作用提供详细信息。虽然网格不均匀溶剂化理论（GIST）能够从显式溶剂分子动力学模拟中提供严格、详细的热力学信息，但最近 3D 参考相互作用位点模型（3D-RISM）理论的发展使得许多相同的量可以在一小部分时间内计算出来。然而，3D-RISM 产生的是原子位点而不是分子密度分布，从原子位点密度分布中很难提取出物理意义。为了克服这一困难，我们引入了一种从原子位点密度分布重建分子密度分布的方法。此外，我们通过分析凝血因子 Xa 与 GIST 和 3D-RISM 的结合位点来评估所得溶剂化热力学密度分布的质量。我们发现，这两种方法在氧和氢密度以及直接的溶质-溶剂能量相互作用方面具有良好的定性一致性。然而，3D-RISM 预测从本体到结合位点移动水的能量和熵罚较低。
