Multiscale multiphysics and multidomain models-Flexibility and rigidity
Multiscale multiphysics and multidomain models-Flexibility and rigidity
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DOI：
10.1063/1.4830404
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发表时间：
2013-11-21
影响因子：
4.4
通讯作者：
Wei, Guo-Wei
中科院分区：
文献类型：
--
作者：
Xia, Kelin;Opron, Kristopher;Wei, Guo-Wei
大型大分子的复杂性给其全尺度理论描述和计算机模拟带来了挑战。引入多尺度多物理场和多域模型，在保持建模精度和实现计算效率的同时减少了自由度的数量。总能量泛函的构建是为了把极性和非极性溶剂化、化学势、流体流动、分子力学和弹性动力学的能量放在一个平等的基础上。利用变分原理推导了上述多物理描述的耦合控制方程。在这些控制方程中，泊松-玻尔兹曼方程描述了带原子电荷的连续统静电。本文介绍了具有原子刚性的连续介质弹性理论。CEWAR的实质是将剪切模量表述为原子刚度的连续函数。因此，将大分子系统的动力学复杂性与其静态复杂性分离开来，用连续介质弹性理论处理耗时较长的动力学问题，而用原子方法进行耗时较短的静态分析。我们提出了一种简单的方法，即柔性-刚性指数（FRI），来分析大分子在原子细节上的柔性和刚性。FRI的构建依赖于一个基本假设，即蛋白质的功能，如柔韧性、刚性和能量，完全由蛋白质的结构及其环境决定，尽管结构反过来又由所有相互作用决定。因此，FRI测量蛋白质原子或残基的拓扑连通性，并表征蛋白质结构的几何紧密性。因此，FRI不依赖于相互作用哈密顿量，并绕过矩阵对角化，这是大多数其他柔性分析方法的基础。FRI的计算复杂度最多为0 (N-2)，其中N为原子数或残基数，而基于哈密顿的方法的计算复杂度为0 （N-3）。我们证明，所提出的FRI可以准确预测263种蛋白质的蛋白质b因子。结果表明，无参数FRI的精度可以达到参数优化后FRI的95%左右，并提出了一种用于可视化和CEWAR的连续原子柔性函数的插值算法。(C) 2013 AIP出版有限责任公司
The emerging complexity of large macromolecules has led to challenges in their full scale theoretical description and computer simulation. Multiscale multiphysics and multidomain models have been introduced to reduce the number of degrees of freedom while maintaining modeling accuracy and achieving computational efficiency. A total energy functional is constructed to put energies for polar and nonpolar solvation, chemical potential, fluid flow, molecular mechanics, and elastic dynamics on an equal footing. The variational principle is utilized to derive coupled governing equations for the above mentioned multiphysical descriptions. Among these governing equations is the Poisson-Boltzmann equation which describes continuum electrostatics with atomic charges. The present work introduces the theory of continuum elasticity with atomic rigidity (CEWAR). The essence of CEWAR is to formulate the shear modulus as a continuous function of atomic rigidity. As a result, the dynamics complexity of a macromolecular system is separated from its static complexity so that the more time-consuming dynamics is handled with continuum elasticity theory, while the less time-consuming static analysis is pursued with atomic approaches. We propose a simple method, flexibility-rigidity index (FRI), to analyze macromolecular flexibility and rigidity in atomic detail. The construction of FRI relies on the fundamental assumption that protein functions, such as flexibility, rigidity, and energy, are entirely determined by the structure of the protein and its environment, although the structure is in turn determined by all the interactions. As such, the FRI measures the topological connectivity of protein atoms or residues and characterizes the geometric compactness of the protein structure. As a consequence, the FRI does not resort to the interaction Hamiltonian and bypasses matrix diagonalization, which underpins most other flexibility analysis methods. FRI's computational complexity is of O(N-2) at most, where N is the number of atoms or residues, in contrast to O(N-3) for Hamiltonian based methods. We demonstrate that the proposed FRI gives rise to accurate prediction of protein B-Factor for a set of 263 proteins. We show that a parameter free FRI is able to achieve about 95% accuracy of the parameter optimized FRI. An interpolation algorithm is developed to construct continuous atomic flexibility functions for visualization and use with CEWAR. (C) 2013 AIP Publishing LLC.