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Int J Mol Sci. 2016 Jan 26;17(2). pii: E144. doi: 10.3390/ijms17020144.

Insights into Protein-Ligand Interactions: Mechanisms, Models, and Methods.

Du X1, Li Y2, Xia YL3, Ai SM4,5, Liang J6, Sang P7,8, Ji XL9,10, Liu SQ11,12.

Author information

1
Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. duxingok@gmail.com.
2
Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. liyi.gerry@gmail.com.
3
Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. xiayl@ynu.edu.cn.
4
Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. aishimann@gmail.com.
5
Department of Applied Mathematics, Yunnan Agricultural University, Kunming 650201, China. aishimann@gmail.com.
6
Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. liangjingyn90@gmail.com.
7
Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. speng431@gmail.com.
8
Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China. speng431@gmail.com.
9
Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. rich@ynu.edu.cn.
10
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.
11
Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China. shuqunliu@ynu.edu.cn.
12
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.

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.

KEYWORDS:

binding driving forces; binding mechanisms; docking; fluorescence polarization (FP); free energy calculations; isothermal titration calorimetry (ITC); kinetics; surface plasmon resonance (SPR); thermodynamics

PMID:
26821017
PMCID:
PMC4783878
DOI:
10.3390/ijms17020144
[Indexed for MEDLINE]
Free PMC Article

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