新型Field-SEA多尺度溶剂模型的开发与应用研究

To develop advanced solvent models and to understand relevant solvent effects are critical for the research fields of chemistry, chemical engineering, drug design, protein engineering and environmental science, where many phenomena and processes take place in solution phase. However, current solvent models usually have some limits, and to develop an accurate, fast and highly transferable solvent model is far from feasible. Such issue is very important for the development of modern molecular simulation and computational chemistry. The applicant developed a fast and accurate multiscale solvent model, Field-SEA, very recently, but much more work are needed to improve this preliminary work. In this project, the applicant plans to improve the accuracy of Field-SEA solvent model, especially the accuracy at different temperatures. On the basis of Field-SEA solvent model, the applicant also plans to develop MM/Field-SEA method to calculate protein-ligand binding affinity, and to develop Field-SEA PMF(Potential of Mean Force)calculation method to study protein-interface adsorption. Briefly, the applicant will continue to work on Field-SEA solvent model in this project, which will help drug design and protein adsorption research, and will provide with insights for the development of multiscale science and technology.

化学化工、药物设计、蛋白质工程、环境等领域内的科研生产涉及到的现象和过程往往在溶液中进行；所以，合适溶剂模型的开发和相关溶剂化效应的理解对它们都有至关重要的意义。然而现有不同尺度上的溶剂模型都有其各自的局限性：其主要问题在于计算效率、精确度、可迁移性之间的矛盾；这也是计算化学和分子模拟进一步发展亟待解决的最基础、关键的问题之一。申请人基于多尺度科研思路，以TIP3P模型为基准开发出准确快速的Field-SEA多尺度溶剂模型；拟在此基础上以TIP4P、AMOEBA为基准重新开发Field-SEA模型，进一步提高模型的精确度尤其是不同温度下的精确度。申请人还拟在Field-SEA模型的基础上，发展MM/Field-SEA蛋白-配体结合自由能计算方法用于药物先导物分子筛选；同时还拟发展Field-SEA PMF(Potential of Mean Force)计算方法用于蛋白质界面吸附研究。

溶剂效应对绝大部分化学反应、化工过程都很重要；所以，理解溶剂效应、开发并合理运用溶剂模型对化学、化工尤其是计算模拟很有科学和实践意义。本项目综合运用量子化学（QM）、分子动力学（MD）、连续介质（COSMO）、宏观热力学（NRTL，CNIBS，UNIQUAC等）等不同尺度的溶剂模型研究了溶质分子固-溶液相分配，水-有机溶剂相分配，以及纳米孔道等多个具有重要化学、化工意义的过程和问题；不仅取得与实验相当符合结果，还指导实验开发了提取提纯药物分子的溶剂、（从工业废水中）萃取酚类溶质的萃取剂；设计基于纳米孔道的水处理膜、设计传质、催化性能优异的介孔MOF(Metal Organic Frame)材料等。这些研究成果在Nat Commun（IF=12.1）、Sci Adv（IF=11.5，Science子刊）、J Mater Chem A（IF=9.93，被遴选为杂志hot papers）、Chem Eng J（IF=6.72，成为ESI高被引论文）等国际知名学术期刊发表SCI论文34篇，并被Advanced Science News（德国Wiley出版集团）、EurekAlert（美国科学促进会AAAS）、《物理化学学报》等二十多家国内外媒体广泛报道。这些成果对化工产品提纯、环境保护、水净化与处理、催化等方面都颇具科研和实践意义。