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Review
. 2016 Jan 26;17(2):144.
doi: 10.3390/ijms17020144.

VSports最新版本 - Insights into Protein-Ligand Interactions: Mechanisms, Models, and Methods

Xing Du  1 , Yi Li  2 , Yuan-Ling Xia  3 , Shi-Meng Ai  4   5 , Jing Liang  6 , Peng Sang  7   8 , Xing-Lai Ji  9   10 , Shu-Qun Liu  11   12
Affiliations
Review

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

"VSports app下载" Xing Du et al. Int J Mol Sci. .

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 VSports手机版. 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 V体育安卓版. .

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Figures

Figure 1
Figure 1
Schematic illustrations of the three protein-ligand binding models: (a) Lock-and-key; (b) Induced fit; and (c) Conformational selection. Adapted from [52].
Figure 2
Figure 2
Representative ITC data for the binding of cytidine 2′-monophosphate (2′CMP) to RNaseA: (a) Primary raw data; (b) Binding curve derived from the raw data. Adapted from [7] Copyright 2008 with permission from Annual Reviews.
Figure 3
Figure 3
Thermodynamic profiles for three pairs of HIV-1 proteinase inhibitors that vary by only a single group: (a) KNI-10033-KNI-10075 pair within which an apolar group thioether on KNI-10033 is replaced by a polar group sulfonyl to form KNI-10075; (b) KNI-10052-KNI-10054 pair within which an apolar methyl group is replaced by a polar hydroxyl group; and (c) KNI-10046-KNI-10030 pair within which a hydrogen atom on the former is replaced by an apolar methyl group to form the latter. The binding free energy (ΔG), enthalpy (ΔH), and entropy (TΔS) are shown. The data shown are taken from [122,127,128].
Figure 3
Figure 3
Thermodynamic profiles for three pairs of HIV-1 proteinase inhibitors that vary by only a single group: (a) KNI-10033-KNI-10075 pair within which an apolar group thioether on KNI-10033 is replaced by a polar group sulfonyl to form KNI-10075; (b) KNI-10052-KNI-10054 pair within which an apolar methyl group is replaced by a polar hydroxyl group; and (c) KNI-10046-KNI-10030 pair within which a hydrogen atom on the former is replaced by an apolar methyl group to form the latter. The binding free energy (ΔG), enthalpy (ΔH), and entropy (TΔS) are shown. The data shown are taken from [122,127,128].
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