Packing optimization for automated generation of complex system's initial configurations for molecular dynamics and docking
Packing optimization for automated generation of complex system's initial configurations for molecular dynamics and docking
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DOI：
10.1002/jcc.10216
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发表时间：
2003-05-01
影响因子：
3
通讯作者：
Martínez, L
中科院分区：
文献类型：
--
作者：
Martínez, JM;Martínez, L
分子动力学是在分子水平上理解许多化学和生物化学系统的一种强有力的方法。为结构和热力学分析开发的理论和技术已经很好地建立起来，并且有许多软件包可用。然而，为动力学设计起始配置可能很麻烦。当研究简单的液体或混合物时，可以使用容易生成的规则晶格。然而，对于复杂的混合物，聚合物溶液或固体吸附液体（例如），这种方法是低效的，并且很难获得足够的坐标文件。在这篇文章中，获得一个适当的初始配置的问题被视为一个“包装”问题，并解决了优化过程。初始构型的选择应使不同分子的原子之间的最小距离大于固定公差。优化使用一个众所周知的算法框约束最小化。生物分子溶剂化，多组分混合物和接口的应用。这种方法可以以自动化的方式将设计初始配置的工作从几天或几周减少到几分钟或几小时。包装优化也被证明是一个强大的空间搜索方法，在对接的小配体蛋白质。这通过甲状腺激素与其核受体的对接来证明。(C)2003 Wiley Periodicals，Inc.
Molecular Dynamics is a powerful methodology for the comprehension at molecular level of many chemical and biochemical systems. The theories and techniques developed for structural and thermodynamic analyses are well established, and many software packages are available. However, designing starting configurations for dynamics can be cumbersome. Easily generated regular lattices can be used when simple liquids or mixtures are studied. However, for complex mixtures, polymer solutions or solid adsorbed liquids (for example) this approach is inefficient, and it turns out to be very hard to obtain an adequate coordinate file. In this article, the problem of obtaining an adequate initial configuration is treated as a "packing" problem and solved by an optimization procedure. The initial configuration is chosen in such a way that the minimum distance between atoms of different molecules is greater than a fixed tolerance. The optimization uses a well-known algorithm for box-constrained minimization. Applications are given for biomolecule solvation, many-component mixtures, and interfaces. This approach can reduce the work of designing starting configurations from days or weeks to few minutes or hours, in an automated fashion. Packing optimization is also shown to be a powerful methodology for space search in docking of small ligands to proteins. This is demonstrated by docking of the thyroid hormone to its nuclear receptor. (C) 2003 Wiley Periodicals, Inc.