Insights into Protein-Ligand Interactions: Mechanisms, Models, and Methods.
Insights into Protein-Ligand Interactions: Mechanisms, Models, and Methods.
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DOI：
10.3390/ijms17020144
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发表时间：
2016-01-26
影响因子：
5.6
通讯作者：
Liu SQ
中科院分区：
文献类型：
--
作者：
Du X;Li Y;Xia YL;Ai SM;Liang J;Sang P;Ji XL;Liu SQ
分子识别是生物大分子之间或各种小分子之间以高度特异性和亲和力相互作用形成特定复合物的过程，是生物体一切过程的基础。蛋白质是一类重要的生物大分子，通过与自身或其他分子结合来实现其功能。因此，对蛋白质-配体相互作用的详细了解对于在分子水平上理解生物学至关重要。此外，对蛋白质-配体识别和结合机制的了解也将促进药物的发现、设计和开发。在本综述中，首先，蛋白质-配体结合的物理化学机制，包括结合动力学，热力学概念和关系，结合驱动力，介绍和合理化。接下来，三个目前存在的蛋白质-配体结合模型的“锁和钥匙”，“诱导适合”，和“构象选择”-进行了描述，并讨论了其基本的热力学机制。最后，研究蛋白质-配体结合亲和力的方法，包括实验和理论/计算方法，进行了介绍，并讨论了它们的优点，缺点和挑战。
Molecular recognition, which is the process of biological macromolecules interacting with each other or various small molecules with a high specificity and affinity to form a specific complex, constitutes the basis of all processes in living organisms. Proteins, an important class of biological macromolecules, realize their functions through binding to themselves or other molecules. A detailed understanding of the protein–ligand interactions is therefore central to understanding biology at the molecular level. Moreover, knowledge of the mechanisms responsible for the protein-ligand recognition and binding will also facilitate the discovery, design, and development of drugs. In the present review, first, the physicochemical mechanisms underlying protein–ligand binding, including the binding kinetics, thermodynamic concepts and relationships, and binding driving forces, are introduced and rationalized. Next, three currently existing protein-ligand binding models—the “lock-and-key”, “induced fit”, and “conformational selection”—are described and their underlying thermodynamic mechanisms are discussed. Finally, the methods available for investigating protein–ligand binding affinity, including experimental and theoretical/computational approaches, are introduced, and their advantages, disadvantages, and challenges are discussed.