Cargando…

Mechanisms of ligand binding

Many processes in chemistry and biology involve interactions of a ligand with its molecular target. Interest in the mechanism governing such interactions has dominated theoretical and experimental analysis for over a century. The interpretation of molecular recognition has evolved from a simple rigi...

Descripción completa

Detalles Bibliográficos
Autor principal: Di Cera, Enrico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AIP Publishing LLC 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714259/
https://www.ncbi.nlm.nih.gov/pubmed/33313600
http://dx.doi.org/10.1063/5.0020997
_version_ 1783618717328867328
author Di Cera, Enrico
author_facet Di Cera, Enrico
author_sort Di Cera, Enrico
collection PubMed
description Many processes in chemistry and biology involve interactions of a ligand with its molecular target. Interest in the mechanism governing such interactions has dominated theoretical and experimental analysis for over a century. The interpretation of molecular recognition has evolved from a simple rigid body association of the ligand with its target to appreciation of the key role played by conformational transitions. Two conceptually distinct descriptions have had a profound impact on our understanding of mechanisms of ligand binding. The first description, referred to as induced fit, assumes that conformational changes follow the initial binding step to optimize the complex between the ligand and its target. The second description, referred to as conformational selection, assumes that the free target exists in multiple conformations in equilibrium and that the ligand selects the optimal one for binding. Both descriptions can be merged into more complex reaction schemes that better describe the functional repertoire of macromolecular systems. This review deals with basic mechanisms of ligand binding, with special emphasis on induced fit, conformational selection, and their mathematical foundations to provide rigorous context for the analysis and interpretation of experimental data. We show that conformational selection is a surprisingly versatile mechanism that includes induced fit as a mathematical special case and even captures kinetic properties of more complex reaction schemes. These features make conformational selection a dominant mechanism of molecular recognition in biology, consistent with the rich conformational landscape accessible to biological macromolecules being unraveled by structural biology.
format Online
Article
Text
id pubmed-7714259
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher AIP Publishing LLC
record_format MEDLINE/PubMed
spelling pubmed-77142592021-03-17 Mechanisms of ligand binding Di Cera, Enrico Biophys Rev Reviews Many processes in chemistry and biology involve interactions of a ligand with its molecular target. Interest in the mechanism governing such interactions has dominated theoretical and experimental analysis for over a century. The interpretation of molecular recognition has evolved from a simple rigid body association of the ligand with its target to appreciation of the key role played by conformational transitions. Two conceptually distinct descriptions have had a profound impact on our understanding of mechanisms of ligand binding. The first description, referred to as induced fit, assumes that conformational changes follow the initial binding step to optimize the complex between the ligand and its target. The second description, referred to as conformational selection, assumes that the free target exists in multiple conformations in equilibrium and that the ligand selects the optimal one for binding. Both descriptions can be merged into more complex reaction schemes that better describe the functional repertoire of macromolecular systems. This review deals with basic mechanisms of ligand binding, with special emphasis on induced fit, conformational selection, and their mathematical foundations to provide rigorous context for the analysis and interpretation of experimental data. We show that conformational selection is a surprisingly versatile mechanism that includes induced fit as a mathematical special case and even captures kinetic properties of more complex reaction schemes. These features make conformational selection a dominant mechanism of molecular recognition in biology, consistent with the rich conformational landscape accessible to biological macromolecules being unraveled by structural biology. AIP Publishing LLC 2020-12 /pmc/articles/PMC7714259/ /pubmed/33313600 http://dx.doi.org/10.1063/5.0020997 Text en © 2020 Author(s). 2688-4089/2020/1(1)/011303/26 All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Reviews
Di Cera, Enrico
Mechanisms of ligand binding
title Mechanisms of ligand binding
title_full Mechanisms of ligand binding
title_fullStr Mechanisms of ligand binding
title_full_unstemmed Mechanisms of ligand binding
title_short Mechanisms of ligand binding
title_sort mechanisms of ligand binding
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714259/
https://www.ncbi.nlm.nih.gov/pubmed/33313600
http://dx.doi.org/10.1063/5.0020997
work_keys_str_mv AT diceraenrico mechanismsofligandbinding