Song Yuhua, Zhang Yongjie, Shen Tongye, Bajaj Chandrajit L, McCammon J Andrew, Baker Nathan A
Department of Biochemistry and Molecular Biophysics, Center for Computational Biology, Washington University in St. Louis, St. Louis, Missouri 63110, USA.
Biophys J. 2004 Apr;86(4):2017-29. doi: 10.1016/S0006-3495(04)74263-0.
This article describes the development and implementation of algorithms to study diffusion in biomolecular systems using continuum mechanics equations. Specifically, finite element methods have been developed to solve the steady-state Smoluchowski equation to calculate ligand binding rate constants for large biomolecules. The resulting software has been validated and applied to mouse acetylcholinesterase. Rates for inhibitor binding to mAChE were calculated at various ionic strengths with several different reaction criteria. The calculated rates were compared with experimental data and show very good agreement when the correct reaction criterion is used. Additionally, these finite element methods require significantly less computational resources than existing particle-based Brownian dynamics methods.
本文描述了使用连续介质力学方程研究生物分子系统中扩散的算法的开发与实现。具体而言，已开发出有限元方法来求解稳态斯莫卢霍夫斯基方程，以计算大型生物分子的配体结合速率常数。所得软件已得到验证，并应用于小鼠乙酰胆碱酯酶。在不同离子强度下，采用几种不同的反应标准计算了抑制剂与mAChE的结合速率。将计算得到的速率与实验数据进行比较，结果表明，当使用正确的反应标准时，二者吻合度很高。此外，与现有的基于粒子的布朗动力学方法相比，这些有限元方法所需的计算资源要少得多。
