Rosenfeld R, Vajda S, DeLisi C
Department of Biomedical Engineering, Boston University, Massachusetts 02215, USA.
Annu Rev Biophys Biomol Struct. 1995;24:677-700. doi: 10.1146/annurev.bb.24.060195.003333.
Docking and design are the major computational steps toward understanding and affecting receptor-ligand interactions. The flexibility of many ligands makes these calculations difficult and requires the development and use of special methods. The need for such tools is illustrated by two examples: the design of protease inhibitors and the analysis and design of peptide antigens binding to specific MHC receptors. We review the computational concepts that have been extended from rigid-body to flexible docking, as well as the following important strategies for flexible docking and design: (a) Monte Carlo/molecular dynamics docking, (b) in-site combinatorial search, (c) ligand build-up, and (d) site mapping and fragment assembly. The use of empirical free energy as a target function is discussed. Due to the rapid development of the methodology, most new methods have been tested on only a limited number of applications and are likely to improve results obtained by more traditional computational or graphic tools.
对接和设计是理解和影响受体-配体相互作用的主要计算步骤。许多配体的灵活性使得这些计算变得困难，需要开发和使用特殊方法。蛋白酶抑制剂的设计以及与特定MHC受体结合的肽抗原的分析和设计这两个例子说明了对此类工具的需求。我们回顾了从刚体对接扩展到柔性对接的计算概念，以及柔性对接和设计的以下重要策略：(a) 蒙特卡罗/分子动力学对接，(b) 原位组合搜索，(c) 配体构建，以及 (d) 位点映射和片段组装。还讨论了使用经验自由能作为目标函数的情况。由于方法学的快速发展，大多数新方法仅在有限数量的应用中进行了测试，并且可能会改进通过更传统的计算或图形工具获得的结果。
