Multi-scale approaches to dynamical transmission of protein allostery

Philip D. Townsend; Thomas L. Rodgers; Ehmke Pohl; Mark R. Wilson; Martin J. Cann; Tom C.B. McLeish

doi:10.1007/978-3-319-21687-4_8

Multi-scale approaches to dynamical transmission of protein allostery

Philip D. Townsend^*, Thomas L. Rodgers, Ehmke Pohl, Mark R. Wilson, Martin J. Cann, Tom C.B. McLeish

^*Corresponding author for this work

Physics

Research output: Chapter in Book/Report/Conference proceeding › Chapter

Abstract

We review the idea that allosteric interactions can be transmitted not by structural switching but by the more subtle route of modulation of the amplitude of thermally-activated global dynamical modes in allosteric proteins. The effect is naturally addressed and explored through coarse-grained models of protein dynamics, but can be linked to atomistic models of substrate binding at the fine scale, and to themodynamic free energies at the macroscopic scale. A remarkable specificity at the residue level emerges: allosteric proteins possess a set of ‘control sites’ whose modification by single-point mutation may alter allosteric free-energies non-perturbatively.

Original language	English
Title of host publication	Physical Biology of Proteins and Peptides
Subtitle of host publication	Theory, Experiment, and Simulation
Publisher	Springer
Pages	141-152
Number of pages	12
ISBN (Electronic)	9783319216874
ISBN (Print)	9783319216867
DOIs	https://doi.org/10.1007/978-3-319-21687-4_8
Publication status	Published - 23 Oct 2015

Keywords

CAP protein
Conformational changes
Elastic network models
Molecular simulation
Multiscale modelling
Normal modes

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10.1007/978-3-319-21687-4_8

Cite this

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AU - Townsend, Philip D.

AU - Rodgers, Thomas L.

AU - Pohl, Ehmke

AU - Wilson, Mark R.

AU - Cann, Martin J.

AU - McLeish, Tom C.B.

PY - 2015/10/23

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AB - We review the idea that allosteric interactions can be transmitted not by structural switching but by the more subtle route of modulation of the amplitude of thermally-activated global dynamical modes in allosteric proteins. The effect is naturally addressed and explored through coarse-grained models of protein dynamics, but can be linked to atomistic models of substrate binding at the fine scale, and to themodynamic free energies at the macroscopic scale. A remarkable specificity at the residue level emerges: allosteric proteins possess a set of ‘control sites’ whose modification by single-point mutation may alter allosteric free-energies non-perturbatively.

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KW - Conformational changes

KW - Elastic network models

KW - Molecular simulation

KW - Multiscale modelling

KW - Normal modes

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BT - Physical Biology of Proteins and Peptides

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ER -

Multi-scale approaches to dynamical transmission of protein allostery

Abstract

Keywords

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