Allostery without conformation change: modelling protein dynamics at multiple scales

McLeish, Thomas C.B.; Rodgers, T.L.; Wilson, Mark R.

doi:10.1088/1478-3975/10/5/056004

Allostery without conformation change: modelling protein dynamics at multiple scales

McLeish, Thomas C.B.; Rodgers, T.L.; Wilson, Mark R.

Authors

Thomas C.B. McLeish

T.L. Rodgers

Professor Mark Wilson mark.wilson@durham.ac.uk
Professor

Abstract

The original ideas of Cooper and Dryden, that allosteric signalling can be induced between distant binding sites on proteins without any change in mean structural conformation, has proved to be a remarkably prescient insight into the rich structure of protein dynamics. It represents an alternative to the celebrated Monod–Wyman–Changeux mechanism and proposes that modulation of the amplitude of thermal fluctuations around a mean structure, rather than shifts in the structure itself, give rise to allostery in ligand binding. In a complementary approach to experiments on real proteins, here we take a theoretical route to identify the necessary structural components of this mechanism. By reviewing and extending an approach that moves from very coarse-grained to more detailed models, we show that, a fundamental requirement for a body supporting fluctuation-induced allostery is a strongly inhomogeneous elastic modulus. This requirement is reflected in many real proteins, where a good approximation of the elastic structure maps strongly coherent domains onto rigid blocks connected by more flexible interface regions.

Citation

McLeish, T. C., Rodgers, T., & Wilson, M. R. (2013). Allostery without conformation change: modelling protein dynamics at multiple scales. Physical Biology, 10(5), https://doi.org/10.1088/1478-3975/10/5/056004

Journal Article Type	Article
Publication Date	Oct 1, 2013
Deposit Date	Jun 14, 2014
Publicly Available Date	Aug 15, 2014
Journal	Physical Biology
Electronic ISSN	1478-3975
Publisher	IOP Publishing
Peer Reviewed	Peer Reviewed
Volume	10
Issue	5
DOI	https://doi.org/10.1088/1478-3975/10/5/056004

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Copyright Statement
© 2013 IOP Publishing Ltd. This is an author-created, un-copyedited version of an article accepted for publication in Physical Biology. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at http://dx.doi.org/10.1088/1478-3975/10/5/056004.