生物分子模拟中静电相互作用计算的新型镜像溶剂模型与高效算法

In computer simulations of bio-macromolecules, it has been a very challenging problem to model the solvent environment surrounding the biomolecule under study in a manner that is physically accurate and computationally efficient at the same time. In this project, based on the most recent developments in methods of images and hybrid explicit/implicit solvation models for electrostatic interactions in biomolecular simulations, the PI proposes to develop more accurate, more efficient, and also more general image-charge solvation models (ICSMs). One major advantage of this type of solvation models lies in the fact that it can be applied to model inhomogeneous systems. First, the PI proposes to incorporate for the first time the three-layer dielectric continuum model into the ICSM so as to further improve the computational efficiency of the ICSM. Second, the PI plans to extend the method of images for the electrostatics calculation in the spherical dielectric cavity to the prolate spheroidal cavity, and then based on which, to develop the ICSM that can model biomolecules of non-spherical shapes more efficiently. Third, the PI proposes to study more general methods of images for calculating ionic solvent induced reaction fields in a spherical cavity, and based on which, to extend the ICSM originally designed for aqueous solutions to ionic solutions. Last, the PI intends to implement the developed novel ICSMs as independent modules compatible with the popular molecular modeling package TINKER. To test and evaluate their correctness and efficiency, the proposed models and algorithms will be used in molecular dynamics simulations of liquid water as well as ions solvated in water. Success of these efforts should have important and far-reaching impact on the state-of-the-art capability in molecular simulations.

在生物大分子的计算机模拟中，如何既物理上精确又计算上高效地模拟生物大分子周围的溶剂环境，一直以来都是一个极具挑战性的难题。本项目拟基于静电相互作用计算的镜像法以及混合显隐溶剂模型领域中的最新研究成果，开发设计更精确、更有效、更通用，并适合异质生物系统模拟的新型镜像溶剂模型（ICSMs）。首先，将三层连续电介质模型结合到ICSM中，建立计算效率更高的三层ICSM。其次，将球腔的镜像法拓展到长椭球状绝缘腔，开发能更有效模拟非球状生物大分子的ICSM。再次，设计离子溶剂感应下反应场的镜像法，开发离子溶剂中生物大分子模拟的ICSM。最后，将各种新型的ICSM实现成与分子建模软件TINKER兼容的独立模块，并通过液态水和溶于水中的离子的分子动力学模拟，来检验和评估所开发模型及相关算法的正确性和有效性。拟建项目所建立的各种新型模型和高效算法将对实际生物系统的计算机模拟产生重要而又深远的影响。

在生物大分子的计算机模拟中，如何既物理上精确又计算上高效地模拟生物大分子周围的溶剂环境，一直以来都是一个极具挑战性的难题。本项目基于静电相互作用计算的镜像法以及混合显隐溶剂模型领域中的最新研究成果，设计了更精确、更有效，并适合异构生物系统模拟的新型镜像溶剂模型。首先，将三层连续电介质模型成功地结合到镜像溶剂模型中，建立了计算效率更高的三层球状模腔镜像溶剂模型。其次，将计算球状绝缘腔内反应场的镜像法拓展到了类球（椭球或扁球）状绝缘腔，建立了类球状模腔镜像溶剂模型。再次，构建了计算圆柱状绝缘腔内反应场的镜像法，建立了圆柱状扩散界面拟调和三层连续电介质模型。然后，对椭球坐标系下拉普拉斯算子的格林函数和诺伊曼函数进行了深入研究，构建了这两种函数的完整镜像系统。接着，对类球调和函数和修正贝塞尔函数的一些重要派生量进行了深入研究，给出了计算这些派生量的精确并稳定的递归算法，并创建了相应的FORTRAN程序包。最后，还将类球状模腔镜像溶剂模型实现成与当前流行的分子建模软件包TINKER兼容的独立程序模块。本项目的研究成果将对实际生物系统的计算机模拟产生重要而又深刻的影响。