Fast and Accurate Numerical Methods of Electrostatic Interactions in Biomolecules

描述(申请人提供)：静电相互作用在分子和细胞过程中发挥着重要作用，包括突触连接的信号传递、离子传输、分子识别以及DNA、RNA和蛋白质的稳定性和功能。最重要的生物学意义是具有不均匀电荷分布的离子、分子和大分子在活细胞的水溶液拥挤环境中的集体行为。这种环境的中心是水，它是一种复杂的溶剂，在离子、分子和水-生物聚合物界面附近具有非本体性质。静电模型作为分子动力学和蒙特卡罗模拟的核心计算，其主要挑战是平衡电荷间相互作用的准确性和现实生物系统所需的效率。对于周期边界效应可以忽略的大系统，Ewald方法是目前最精确的方法。不幸的是，大分子的模拟需要很大的模拟体积，这使得Ewald方法和类似的方法太昂贵，而较小的系统尺寸会影响精度。同时，用连续介质静电学模拟溶剂的速度要快得多，但由于忽略了分子尺度的不均匀性，如溶质表面附近的原子细节，精度受到了影响。

DESCRIPTION (provided by applicant): Electrostatic interactions play an essential role in molecular and cellular processes that include signal transmission at synaptic junctions, ion-transport, molecular recognition, and stability and function of DNA, RNA and proteins. Of paramount biological importance is the collective behavior of ions, molecules, and macromolecules having inhomogeneous charge distributions in the aqueous crowded environment of a living cell. Central to this environment is water, which is a complex solvent with non-bulk properties near ions, molecules and water-biopolymer interfaces. The main challenge for modeling electrostatics, as the core calculation of Molecular Dynamics and Monte Carlo simulations, is to balance the accuracy of interactions among charges and the efficiency required for realistic biological systems. For all-atom simulations the Ewald method is currently the most accurate method for large enough system where periodic boundary effects are negligible. Unfortunately, the simulation of a macromolecule requires a large simulation volume, making the Ewald method and similar methods too expensive while a smaller system size compromises accuracy. Meanwhile, modeling the solvent using continuum electrostatics is much faster, but accuracy is compromised by neglecting molecular scale inhomogeneity, such as atomic details near the surface of the solute.