FAST INTEGRAL METHOD FOR THE POISSON-BOLTZMANN EQUATION

第一阶段的工作成功地发展了一种快速边界元方法(BEM)来求解离子溶液中生物分子的线性Poisson-Boltzmann方程(PBE)。与以往仅限于泊松方程(对应于零离子强度)的快速边界元不同，新的边界元考虑了离子强度效应，从而代表了生物分子模拟的重大进展。在容易接近的工作站上成功地处理了涉及多达80,000个边界元素的问题。在第二阶段，这一新功能将扩展到求解非线性PBE，有效地将PBE解与分子动力学(MD)程序耦合，并模拟多个相对运动的分子。为进一步提高精度和减少计算要求而设计的建模增强也将被纳入，包括一种用于近表面电荷相互作用的新的局部校正方法。第二阶段开发的快速并行边界元分析将得到扩展，以适应这些新功能。为了促进强大的商业化前景，输入/输出将配置为与现有的MD和分子表面生成程序对接。快速边界元PBE解算器将应用于以前无法访问的大规模生物分子系统，重点是推进基础生物学研究和展示快速非线性PBE分析的建模能力。拟议的商业应用：成功完成第二阶段的工作将产生新的强大的计算工具，以解决由线性/非线性泊松/泊松/玻尔兹曼偏微分方程管理的大量应用。由此产生的软件工具将使政府、学术界和工业界的研究人员能够在工作站或PC上对大规模生物系统进行准确的静电建模研究。从这类研究中获得的知识将对制药和生物医学界有价值。

The Phase I effort successfully developed a fast boundary element method (BEM) to solve the linear Poisson-Boltzmann equation (PBE) for biomolecules immersed in ionic solution. Unlike previous fast BEMs which were limited to the Poisson equation (corresponding to zero ionic strength), the new BEM accommodates ionic strength effects and thus represents a major advance in biomolecular modeling. Problems involving up to 80,000 boundary elements were successfully carried out upon readily accessibly workstations. In Phase II, this new capability will be extended to solve the nonlinear PBE, efficiently couple the PBE solutions to molecular dynamics (MD) codes and model multiple molecules in relative motion. Modeling enhancements designed to further improve accuracy and reduce computational requirements will also be incorporated, including a novel local correction method for close surface-charge interactions. The fast parallel BEM analysis developed in Phase II will be extended to accommodate these new capabilities. To promote strong commercialization prospects, the input/output will be configured to interface with existing MD and molecular surface generation codes. The fast BEM PBE solver will be applied to large-scale biomolecular systems that have been previous inaccessible with emphasis upon advancing basic biological research and demonstrating the modeling capabilities of the fast nonlinear PBE analysis. PROPOSED COMMERCIAL APPLICATIONS: Successful completion of the Phase II effort will result in new powerful computational tools to address an enormous range of applications governed by the linear/nonlinear Poisson/Poisson/Boltzmann PDEs. The resulting software tools will allow researchers in government, academia and industry to carry out accurate electrostatic modeling studies of the large-scale biological systems on workstations or PCs. The knowledge gained from such studies will be valuable to the pharmaceutical and biomedical community.