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A non-equilibrium approach to allosteric communication


Stock, Gerhard; Hamm, Peter (2018). A non-equilibrium approach to allosteric communication. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 373(1749):20170187.

Abstract

While the theory of protein folding is well developed, including concepts such as rugged energy landscape, folding funnel, etc., the same degree of understanding has not been reached for the description of the dynamics of allosteric transitions in proteins. This is not only due to the small size of the structural change upon ligand binding to an allosteric site, but also due to challenges in designing experiments that directly observe such an allosteric transition. On the basis of recent pump-probe-type experiments (Buchli et al. 2013 Proc. Natl Acad. Sci. USA110, 11 725–11 730. (doi:10.1073/pnas.1306323110)) and non-equilibrium molecular dynamics simulations (Buchenberg et al. 2017 Proc. Natl Acad. Sci. USA114, E6804–E6811. (doi:10.1073/pnas.1707694114)) studying an photoswitchable PDZ2 domain as model for an allosteric transition, we outline in this perspective how such a description of allosteric communication might look. That is, calculating the dynamical content of both experiment and simulation (which agree remarkably well with each other), we find that allosteric communication shares some properties with downhill folding, except that it is an ‘order–order’ transition. Discussing the multiscale and hierarchical features of the dynamics, the validity of linear response theory as well as the meaning of ‘allosteric pathways’, we conclude that non-equilibrium experiments and simulations are a promising way to study dynamical aspects of allostery.

Abstract

While the theory of protein folding is well developed, including concepts such as rugged energy landscape, folding funnel, etc., the same degree of understanding has not been reached for the description of the dynamics of allosteric transitions in proteins. This is not only due to the small size of the structural change upon ligand binding to an allosteric site, but also due to challenges in designing experiments that directly observe such an allosteric transition. On the basis of recent pump-probe-type experiments (Buchli et al. 2013 Proc. Natl Acad. Sci. USA110, 11 725–11 730. (doi:10.1073/pnas.1306323110)) and non-equilibrium molecular dynamics simulations (Buchenberg et al. 2017 Proc. Natl Acad. Sci. USA114, E6804–E6811. (doi:10.1073/pnas.1707694114)) studying an photoswitchable PDZ2 domain as model for an allosteric transition, we outline in this perspective how such a description of allosteric communication might look. That is, calculating the dynamical content of both experiment and simulation (which agree remarkably well with each other), we find that allosteric communication shares some properties with downhill folding, except that it is an ‘order–order’ transition. Discussing the multiscale and hierarchical features of the dynamics, the validity of linear response theory as well as the meaning of ‘allosteric pathways’, we conclude that non-equilibrium experiments and simulations are a promising way to study dynamical aspects of allostery.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Life Sciences > General Biochemistry, Genetics and Molecular Biology
Life Sciences > General Agricultural and Biological Sciences
Uncontrolled Keywords:General Biochemistry, Genetics and Molecular Biology, General Agricultural and Biological Sciences
Language:English
Date:19 June 2018
Deposited On:30 Aug 2019 11:44
Last Modified:29 Jul 2020 11:15
Publisher:Royal Society Publishing
ISSN:0962-8436
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1098/rstb.2017.0187
Project Information:
  • : FunderEuropean Research Council (ERC)
  • : Grant ID
  • : Project TitleAdvanced Investigator Grant (DYNALLO)
  • : FunderSwiss National Science Foundation
  • : Grant ID
  • : Project TitleNCCR MUST
  • : FunderDeutsche Forschungsgemeinschaft
  • : Grant IDSTO 247/10
  • : Project Title
  • : FunderSwiss National Science Foundation (SNF)
  • : Grant ID200021 165789/1
  • : Project Title

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