Department of Science and Engineering, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan.
J Phys Chem B. 2013 Jun 6;117(22):6718-23. doi: 10.1021/jp4046116. Epub 2013 May 29.
We derive, implement, and apply equilibrium solvation site analysis for biomolecules. Our method utilizes 3D-RISM calculations to quickly obtain equilibrium solvent distributions without either necessity of simulation or limits of solvent sampling. Our analysis of these distributions extracts highest likelihood poses of solvent as well as localized entropies, enthalpies, and solvation free energies. We demonstrate our method on a structure of HIV-1 protease where excellent structural and thermodynamic data are available for comparison. Our results, obtained within minutes, show systematic agreement with available experimental data. Further, our results are in good agreement with established simulation-based solvent analysis methods. This method can be used not only for visual analysis of active site solvation but also for virtual screening methods and experimental refinement.
我们开发、实现并应用了生物分子的平衡溶剂化位点分析方法。我们的方法利用 3D-RISM 计算，在无需模拟或溶剂采样限制的情况下，快速获得平衡溶剂分布。我们对这些分布的分析提取了溶剂的最大可能构象以及局部熵、焓和溶剂化自由能。我们在 HIV-1 蛋白酶的结构上演示了我们的方法，该结构有可用于比较的优异结构和热力学数据。我们在几分钟内获得的结果与可用的实验数据系统一致。此外，我们的结果与基于已建立模拟的溶剂分析方法也非常吻合。这种方法不仅可用于活性位点溶剂化的可视化分析，还可用于虚拟筛选方法和实验优化。
