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

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 macr...

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Autores principales: Du, Xing, Li, Yi, Xia, Yuan-Ling, Ai, Shi-Meng, Liang, Jing, Sang, Peng, Ji, Xing-Lai, Liu, Shu-Qun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783878/
https://www.ncbi.nlm.nih.gov/pubmed/26821017
http://dx.doi.org/10.3390/ijms17020144
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author Du, Xing
Li, Yi
Xia, Yuan-Ling
Ai, Shi-Meng
Liang, Jing
Sang, Peng
Ji, Xing-Lai
Liu, Shu-Qun
author_facet Du, Xing
Li, Yi
Xia, Yuan-Ling
Ai, Shi-Meng
Liang, Jing
Sang, Peng
Ji, Xing-Lai
Liu, Shu-Qun
author_sort Du, Xing
collection PubMed
description 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.
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spelling pubmed-47838782016-03-14 Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods Du, Xing Li, Yi Xia, Yuan-Ling Ai, Shi-Meng Liang, Jing Sang, Peng Ji, Xing-Lai Liu, Shu-Qun Int J Mol Sci Review 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. MDPI 2016-01-26 /pmc/articles/PMC4783878/ /pubmed/26821017 http://dx.doi.org/10.3390/ijms17020144 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Du, Xing
Li, Yi
Xia, Yuan-Ling
Ai, Shi-Meng
Liang, Jing
Sang, Peng
Ji, Xing-Lai
Liu, Shu-Qun
Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods
title Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods
title_full Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods
title_fullStr Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods
title_full_unstemmed Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods
title_short Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods
title_sort insights into protein–ligand interactions: mechanisms, models, and methods
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783878/
https://www.ncbi.nlm.nih.gov/pubmed/26821017
http://dx.doi.org/10.3390/ijms17020144
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