Chasing long-range evolutionary couplings in the AlphaFold era
Author(s)
Karamanos, Theodoros K
Type
Journal Article
Abstract
Coevolution between protein residues is normally interpreted as direct contact. However, the evolutionary record of a protein sequence contains rich information that may include long-range functional couplings, couplings that report on homo-oligomeric states or even conformational changes. Due to the complexity of the sequence space and the lack of structural information on various members of a protein family, it has been difficult to effectively mine the additional information encoded in a multiple sequence alignment (MSA). Here, taking advantage of the recent release of the AlphaFold (AF) database we attempt to identify coevolutionary couplings that cannot be explained simply by spatial proximity. We propose a simple computational method that performs direct coupling analysis on a MSA and searches for couplings that are not satisfied in any of the AF models of members of the identified protein family. Application of this method on 2012 protein families suggests that ~12% of the total identified coevolving residue pairs are spatially distant and more likely to be disordered than their contacting counterparts. We expect that this analysis will help improve the quality of coevolutionary distance restraints used for structure determination and will be useful in identifying potentially functional/allosteric cross-talk between distant residues.
Date Issued
2023-03
Date Acceptance
2023-01-27
Citation
Biopolymers, 2023, 114 (3), pp.1-8
ISSN
0006-3525
Publisher
Wiley
Start Page
1
End Page
8
Journal / Book Title
Biopolymers
Volume
114
Issue
3
Copyright Statement
© 2023 The Author. Biopolymers published by Wiley Periodicals LLC.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Wellcome Trust
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000931213300001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
223268/Z/21/Z
Subjects
AlphaFold
Biochemistry & Molecular Biology
Biophysics
coevolution
COEVOLUTION
computational biology
DIRECT RESIDUE CONTACTS
DOMAIN
IDENTIFICATION
INTER-PROTEIN
intrinsically disordered proteins
Life Sciences & Biomedicine
MODULATION
NETWORKS
PREDICTION
protein structure
PROTEIN-INTERACTION
Science & Technology
SEQUENCE
Publication Status
Published
Article Number
ARTN e23530
Date Publish Online
2023-02-08