Affiliation:
1. Biomolecular Dynamics, Institute of Physics, Albert Ludwigs University, Freiburg, Germany
2. Department of Chemistry, University of Zurich, Zurich, Switzerland
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. USA
110
, 11 725–11 730. (
doi:10.1073/pnas.1306323110
)) and non-equilibrium molecular dynamics simulations (Buchenberg
et al.
2017
Proc. Natl Acad. Sci. USA
114
, 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.
This article is part of a discussion meeting issue ‘Allostery and molecular machines’.
Funder
Deutsche Forschungsgemeinschaft
H2020 European Research Council
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology
Cited by
48 articles.
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