dorsal/arxiv
View SchemaLigand Binding, Protein Fluctuations, and Allosteric Free Energy
| Authors | Michael E. Wall |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0603027 |
| URL | https://arxiv.org/abs/q-bio/0603027 |
| DOI | 10.1063/1.2345620 |
Abstract
Although the importance of protein dynamics in protein function is generally recognized, the role of protein fluctuations in allosteric effects scarcely has been considered. To address this gap, the Kullback-Leibler divergence (Dx) between protein conformational distributions before and after ligand binding was proposed as a means of quantifying allosteric effects in proteins. Here, previous applications of Dx to methods for analysis and simulation of proteins are first reviewed, and their implications for understanding aspects of protein function and protein evolution are discussed. Next, equations for Dx suggest that k_{B}TDx should be interpreted as an allosteric free energy -- the free energy associated with changing the ligand-free protein conformational distribution to the ligand-bound conformational distribution. This interpretation leads to a thermodynamic model of allosteric transitions that unifies existing perspectives on the relation between ligand binding and changes in protein conformational distributions. The definition of Dx is used to explore some interesting mathematical relations among commonly recognized thermodynamic and biophysical quantities, such as the total free energy change upon ligand binding, and ligand-binding affinities for individual protein conformations. These results represent the beginnings of a theoretical framework for considering the full protein conformational distribution in modeling allosteric transitions. Early applications of the framework have produced results with implications both for methods for coarsed-grained modeling of proteins, and for understanding the relation between ligand binding and protein dynamics.
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"abstract": "Although the importance of protein dynamics in protein function is generally\nrecognized, the role of protein fluctuations in allosteric effects scarcely has\nbeen considered. To address this gap, the Kullback-Leibler divergence (Dx)\nbetween protein conformational distributions before and after ligand binding\nwas proposed as a means of quantifying allosteric effects in proteins. Here,\nprevious applications of Dx to methods for analysis and simulation of proteins\nare first reviewed, and their implications for understanding aspects of protein\nfunction and protein evolution are discussed. Next, equations for Dx suggest\nthat k_{B}TDx should be interpreted as an allosteric free energy -- the free\nenergy associated with changing the ligand-free protein conformational\ndistribution to the ligand-bound conformational distribution. This\ninterpretation leads to a thermodynamic model of allosteric transitions that\nunifies existing perspectives on the relation between ligand binding and\nchanges in protein conformational distributions. The definition of Dx is used\nto explore some interesting mathematical relations among commonly recognized\nthermodynamic and biophysical quantities, such as the total free energy change\nupon ligand binding, and ligand-binding affinities for individual protein\nconformations. These results represent the beginnings of a theoretical\nframework for considering the full protein conformational distribution in\nmodeling allosteric transitions. Early applications of the framework have\nproduced results with implications both for methods for coarsed-grained\nmodeling of proteins, and for understanding the relation between ligand binding\nand protein dynamics.",
"arxiv_id": "q-bio/0603027",
"authors": [
"Michael E. Wall"
],
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"q-bio.BM",
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"doi": "10.1063/1.2345620",
"title": "Ligand Binding, Protein Fluctuations, and Allosteric Free Energy",
"url": "https://arxiv.org/abs/q-bio/0603027"
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