Cited by 73Protein Structure and DynamicsReceptor Mechanisms and SignalingProtein Interaction Studies and Fluorescence Analysis

Mechanisms of ligand binding

Open access
Di Cera, Enrico·2020·Biophysics Reviews

Abstract

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.

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Crossref · 10.1063/5.0020997

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  • AlphaFold, which predicts single ranked structures for a protein sequence, is unable to address directly allosteric mechanisms, which are based on populations of conformational states in ensembles.

    “AlphaFold, which predicts single ranked structures for a protein sequence, is unable to address directly allosteric mechanisms, which are based on the populations of conformational states in the ensembles.”

    From AlphaFold, Artificial Intelligence (AI), and Allostery (2022) · cites this paper as [108]

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Research works printed but not linked: 3

  1. [23]H. Gutfreund, Kinetics for the Life Sciences: Receptors, Transmitters and Catalysts (Cambridge University Press, Cambridge, 1995).
  2. [24]T. L. Hill, Free Energy Transduction in Biology (Academic Press, New York, 1977).
  3. [30]E. Di Cera, Thermodynamic Theory of Site-Specific Binding Processes in Biological Macromolecules (Cambridge University Press, Cambridge, 1995).

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Authors
Di Cera, E.
Affiliations
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine , St. Louis, Missouri 63104, USA
Venue
Biophysics Reviews
Published
2020-11-16
Volume
1
Issue
1
Pages
011303-011303
ISSN
2688-4089 (ISSN-L)
OpenAlex
W3105542907
Cited by
73
References
181
Citations by year
2026: 12 · 2025: 17 · 2024: 15 · 2023: 6 · 2022: 11 · 2021: 10 · 2020: 2
FWCI
0.69
Type
journal article
Language
en
Open access
Locations
  • Biophysics Reviews (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (HL049413, HL139554, HL147821)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
Keywords
ligand binding, induced fit, conformational selection, molecular recognition, conformational change, binding kinetics, reaction scheme, free energy landscape, protein-ligand interactions, conformational equilibrium

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