Simulation of biomolecular diffusion and complex formation.
Simulation of biomolecular diffusion and complex formation.
复制标题
生物分子扩散和复合物形成的模拟。
DOI：
10.1016/s0006-3495(86)83632-3
复制
发表时间：
1986
影响因子：
3.4
通讯作者：
McCammon,JA
中科院分区：
文献类型：
--
作者：
Allison,SA;Northrup,SH;McCammon,JA
扩散是分子生物物理学中非常广泛重要的现象。扩散可以确定多亚基结构组装的速率和特征、配体与受体的结合以及涉及溶剂表面位移的分子和组装体的内部运动。当前的计算机模拟技术提供了比过去更详细的扩散过程描述。可以构建模型以包含诸如亚分子水平的结构亚基（域、单体或原子）等现实特征；详细的静电荷分布和相应的溶剂筛选的分子间和分子内相互作用；和流体动力相互作用。可以分析轨迹以提供有关生物分子功能的直接信息（例如，两种蛋白质之间形成电子转移复合物的双分子速率常数），或者提供或测试用于解释实验数据的模型（例如，DNA片段的荧光去极化的时间依赖性）。在这里，我们首先回顾扩散模拟理论，特别强调新技术，例如获得柔性组件的传输特性和扩散控制反应的速率常数的技术。然后我们调查了最近的各种应用，包括 DNA 片段大规模运动和酶-底物结合中底物“操纵”的研究。我们最后讨论了当前的工作（例如蛋白质复合物的形成）和未来工作的可能领域。
Diffusion is a phenomenon of very widespread importance in molecular biophysics. Diffusion can determine the rates and character of the assembly of multisubunit structures, the binding of ligands to receptors, and the internal motions of molecules and assemblies that involve solvent surface displacements. Current computer simulation techniques provide much more detailed descriptions of diffusional processes than have been available in the past. Models can be constructed to include such realistic features as structural subunits at the submolecular level (domains, monomers, or atoms); detailed electrostatic charge distributions and corresponding solvent-screened inter- and intramolecular interactions; and hydrodynamic interactions. The trajectories can be analyzed either to provide direct information on biomolecular function (e.g., the bimolecular rate constant for formation of an electron-transfer complex between two proteins), or to provide or test models for the interpretation of experimental data (e.g., the time dependence of fluorescence depolarization for segments of DNA). Here, we first review the theory of diffusional simulations, with special emphasis on new techniques such as those for obtaining transport properties of flexible assemblies and rate constants of diffusion-controlled reactions. Then we survey a variety of recent applications, including studies of large-scale motion in DNA segments and substrate "steering" in enzyme-substrate binding. We conclude with a discussion of current work (e.g., formation of protein complexes) and possible areas for future work.