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Licensed Unlicensed Requires Authentication Published by De Gruyter November 27, 2014

Opportunities and limitations in applying coevolution-derived contacts to protein structure prediction

  • Stuart Tetchner , Tomasz Kosciolek ORCID logo and David T. Jones EMAIL logo


The prospect of identifying contacts in protein structures purely from aligned protein sequences has lured researchers for a long time, but progress has been modest until recently. Here, we reviewed the most successful methods for identifying structural contacts from sequence and how these methods differ and made an initial assessment of the overlap of predicted contacts by alternative approaches. We then discussed the limitations of these methods and possibilities for future development and highlighted the recent applications of contacts in tertiary structure prediction, identifying the residues at the interfaces of protein-protein interactions, and the use of these methods in disentangling alternative conformational states. Finally, we identified the current challenges in the field of contact prediction, concentrating on the limitations imposed by available data, dependencies on the sequence alignments, and possible future developments.

Corresponding author: David T. Jones, Department of Computer Science, University College London, London WC1E 6BT, UK, E-mail:


The authors thank Domenico Cozzetto for useful discussions. ST and TK were supported by the Wellcome Trust (studentship numbers 096622/Z/11/Z and 096624/Z/11/Z, respectively).

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


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Received: 2014-8-11
Accepted: 2014-10-15
Published Online: 2014-11-27
Published in Print: 2014-12-19

©2014 by De Gruyter

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