Warshel Arieh, Sharma Pankaz K, Kato Mitsunori, Parson William W
University of Southern California, 418 SGM Building, 3620 McClintock Avenue, Los Angeles, CA 90089-1062, USA.
Biochim Biophys Acta. 2006 Nov;1764(11):1647-76. doi: 10.1016/j.bbapap.2006.08.007. Epub 2006 Aug 25.
Electrostatic energies provide what is perhaps the most effective tool for structure-function correlation of biological molecules. This review considers the current state of simulations of electrostatic energies in macromolecules as well as the early developments of this field. We focus on the relationship between microscopic and macroscopic models, considering the convergence problems of the microscopic models and the fact that the dielectric 'constants' in semimacroscopic models depend on the definition and the specific treatment. The advances and the challenges in the field are illustrated considering a wide range of functional properties including pK(a)'s, redox potentials, ion and proton channels, enzyme catalysis, ligand binding and protein stability. We conclude by pointing out that, despite the current problems and the significant misunderstandings in the field, there is an overall progress that should lead eventually to quantitative descriptions of electrostatic effects in proteins and thus to quantitative descriptions of the function of proteins.
静电能为生物分子的结构-功能相关性研究提供了或许最为有效的工具。本文综述了大分子静电能模拟的当前状况以及该领域的早期发展。我们着重探讨微观模型与宏观模型之间的关系，考虑微观模型的收敛问题以及半宏观模型中的介电“常数”取决于定义和具体处理方式这一事实。通过考虑包括pK(a)值、氧化还原电位、离子和质子通道、酶催化、配体结合以及蛋白质稳定性等广泛的功能特性，阐述了该领域的进展与挑战。我们指出，尽管该领域目前存在问题和重大误解，但总体上仍有进展，最终应能实现对蛋白质静电效应的定量描述，进而实现对蛋白质功能的定量描述。
