Direct coupling analysis of epistasis in allosteric materials
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Published version
Author(s)
Bravi, Barbara
Ravasio, Riccardo
Brito, Carolina
Wyart, Matthieu
Type
Journal Article
Abstract
In allosteric proteins, the binding of a ligand modifies function at a distant active site. Such allosteric pathways can be used as target for drug design, generating considerable interest in inferring them from sequence alignment data. Currently, different methods lead to conflicting results, in particular on the existence of long-range evolutionary couplings between distant amino-acids mediating allostery. Here we propose a resolution of this conundrum, by studying epistasis and its inference in models where an allosteric material is evolved in silico to perform a mechanical task. We find in our model the four types of epistasis (Synergistic, Sign, Antagonistic, Saturation), which can be both short or long-range and have a simple mechanical interpretation. We perform a Direct Coupling Analysis (DCA) and find that DCA predicts well the cost of point mutations but is a rather poor generative model. Strikingly, it can predict short-range epistasis but fails to capture long-range epistasis, in consistence with empirical findings. We propose that such failure is generic when function requires subparts to work in concert. We illustrate this idea with a simple model, which suggests that other methods may be better suited to capture long-range effects.
Date Issued
2020-03-01
Date Acceptance
2020-01-03
Citation
PLoS Computational Biology, 2020, 16 (3), pp.1-19
ISSN
1553-734X
Publisher
Public Library of Science (PLoS)
Start Page
1
End Page
19
Journal / Book Title
PLoS Computational Biology
Volume
16
Issue
3
Copyright Statement
© 2020 Bravi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000523480200038&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemical Research Methods
Mathematical & Computational Biology
Biochemistry & Molecular Biology
BENEFICIAL MUTATIONS
PROTEIN
NETWORKS
COMMUNICATION
COEVOLUTION
EVOLUTION
DYNAMICS
Publication Status
Published
Article Number
ARTN e1007630
Date Publish Online
2020-03-02