Computational methods to predict binding free energy in ligand-receptor complexes
Computational methods to predict binding free energy in ligand-receptor complexes
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DOI：
10.1021/jm00026a001
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发表时间：
1995-12-22
影响因子：
7.3
通讯作者：
Murcko, MA
中科院分区：
文献类型：
--
作者：
Ajay;Murcko, MA
大多数生物过程依赖于分子之间的结合和区分能力。在生物大分子反应中，形成非共价复合物的能力是普遍存在的。这种关联对于许多功能都是必不可少的，1例如，催化、运输或信号转导。在过去的三十年中收集的结构信息帮助我们在分子水平上理解了许多复合物，提供了受体与其配体之间相互作用的详细描述。结合可以对结构上的微小差异非常敏感。因此，结合过程的定量知识对于理解分子识别是必不可少的。这种定量的知识要求（1）对相互作用中所涉及的物理力有详细的了解，（2）对这些力在整个反应过程中所起的作用有多大的量度。热力学控制着分子识别的基本物理原理。因此，两个或多个分子结合的基本过程与蛋白质折叠的基本过程相似。然而，与折叠相比，结合应该是一个更简单的问题，因为涉及的氨基酸数量较少（10-30），主要在活性位点。形成非共价键的两个分子的亲和力
Most biological processes depend on the ability of molecules to bind and discriminate between one an-other. The ability to form noncovalent complexes is ubiquitous in reactions among biological macromol-ecules. This associationis essential for many functions, 1 eg., catalysis, transport, or signal transduction. Structural information gathered over the past three decades has helped us understand many complexes at the molecular level providing a detailed description of the interaction between a receptor and its ligands. Binding can be remarkably sensitive to even small differences in structure. A quantitative knowledge of the binding process is therefore essential to understand-ing molecular recognition. Such a quantitative knowl-edge requires (1) a detailed understanding of the physical forces involved in the interaction and (2) a measure of the extent to which these forces contribute to the overall reaction procedure.Thermodynamics governs the basic physical prin-ciples of molecular recognition. Therefore, the fundamentals processes involved in the binding of two or more molecules are similar to those for the folding of proteins. Binding, however, should be a simpler problem com-pared to folding as a smaller number (10—30) of amino acids, mostly in the active site, are involved. The affinity of two molecules that form a noncovalent