Geng Weihua, Wei G W
Department of Mathematics, Michigan State University, East Lansing, MI 48824, USA.
J Comput Phys. 2011 Jan 20;230(2):435-457. doi: 10.1016/j.jcp.2010.09.031.
The Poisson-Boltzmann (PB) equation is an established multiscale model for electrostatic analysis of biomolecules and other dielectric systems. PB based molecular dynamics (MD) approach has a potential to tackle large biological systems. Obstacles that hinder the current development of PB based MD methods are concerns in accuracy, stability, efficiency and reliability. The presence of complex solvent-solute interface, geometric singularities and charge singularities leads to challenges in the numerical solution of the PB equation and electrostatic force evaluation in PB based MD methods. Recently, the matched interface and boundary (MIB) method has been utilized to develop the first second order accurate PB solver that is numerically stable in dealing with discontinuous dielectric coefficients, complex geometric singularities and singular source charges. The present work develops the PB based MD approach using the MIB method. New formulation of electrostatic forces is derived to allow the use of sharp molecular surfaces. Accurate reaction field forces are obtained by directly differentiating the electrostatic potential. Dielectric boundary forces are evaluated at the solvent-solute interface using an accurate Cartesian-grid surface integration method. The electrostatic forces located at reentrant surfaces are appropriately assigned to related atoms. Extensive numerical tests are carried out to validate the accuracy and stability of the present electrostatic force calculation. The new PB based MD method is implemented in conjunction with the AMBER package. MIB based MD simulations of biomolecules are demonstrated via a few example systems.
泊松-玻尔兹曼(PB)方程是用于生物分子和其他介电系统静电分析的成熟多尺度模型。基于PB的分子动力学(MD)方法有潜力处理大型生物系统。阻碍当前基于PB的MD方法发展的障碍在于准确性、稳定性、效率和可靠性方面的问题。复杂的溶剂-溶质界面、几何奇点和电荷奇点的存在给PB方程的数值求解以及基于PB的MD方法中的静电力评估带来了挑战。最近,匹配界面和边界(MIB)方法已被用于开发首个二阶精确的PB求解器,该求解器在处理不连续介电系数、复杂几何奇点和奇异源电荷时在数值上是稳定的。目前的工作使用MIB方法开发了基于PB的MD方法。推导了静电力的新公式,以允许使用清晰的分子表面。通过直接对静电势求导获得精确的反应场力。使用精确的笛卡尔网格表面积分方法在溶剂-溶质界面处评估介电边界力。位于凹角表面的静电力被适当地分配给相关原子。进行了广泛的数值测试以验证当前静电力计算的准确性和稳定性。新的基于PB的MD方法与AMBER软件包结合实现。通过几个示例系统展示了基于MIB的生物分子MD模拟。