title: Insights into Protein-Ligand Interactions: Mechanisms, Models, and Methods.
abstract: 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.
authors.affiliation: Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. duxingok@gmail.com.
authors.forename: Xing
authors.initials: X
authors.lastname: Du
authors.affiliation: Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. liyi.gerry@gmail.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. xiayl@ynu.edu.cn.
authors.forename: Yuan-Ling
authors.initials: YL
authors.lastname: Xia
authors.affiliation: Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. aishimann@gmail.com.|Department of Applied Mathematics, Yunnan Agricultural University, Kunming 650201, China. aishimann@gmail.com.
authors.forename: Shi-Meng
authors.initials: SM
authors.lastname: Ai
authors.affiliation: Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. liangjingyn90@gmail.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Liang
authors.affiliation: Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. speng431@gmail.com.|Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China. speng431@gmail.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Sang
authors.affiliation: Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. rich@ynu.edu.cn.|Key Laboratory for Tumor molecular biology of High Education in Yunnan Province, School of Life Sciences, Yunnan University, Kunming 650091, China. rich@ynu.edu.cn.
authors.forename: Xing-Lai
authors.initials: XL
authors.lastname: Ji
authors.affiliation: Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. shuqunliu@ynu.edu.cn.|Key Laboratory for Tumor molecular biology of High Education in Yunnan Province, School of Life Sciences, Yunnan University, Kunming 650091, China. shuqunliu@ynu.edu.cn.
authors.forename: Shu-Qun
authors.initials: SQ
authors.lastname: Liu
mesh_terms: D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D055808:Drug Discovery; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins
keywords: binding driving forces; binding mechanisms; docking; fluorescence polarization (FP); free energy calculations; isothermal titration calorimetry (ITC); kinetics; surface plasmon resonance (SPR); thermodynamics
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