Codon-level information improves predictions of inter-residue contacts in proteins by correlated mutation analysis

Methods for analysing correlated mutations in proteins are becoming an increasingly powerful tool for predicting contacts within and between proteins. Nevertheless, limitations remain due to the requirement for large multiple sequence alignments (MSA) and the fact that, in general, only the relative...

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Main Authors: Etai Jacob, Ron Unger, Amnon Horovitz
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2015-09-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/08932
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author Etai Jacob
Ron Unger
Amnon Horovitz
author_facet Etai Jacob
Ron Unger
Amnon Horovitz
author_sort Etai Jacob
collection DOAJ
description Methods for analysing correlated mutations in proteins are becoming an increasingly powerful tool for predicting contacts within and between proteins. Nevertheless, limitations remain due to the requirement for large multiple sequence alignments (MSA) and the fact that, in general, only the relatively small number of top-ranking predictions are reliable. To date, methods for analysing correlated mutations have relied exclusively on amino acid MSAs as inputs. Here, we describe a new approach for analysing correlated mutations that is based on combined analysis of amino acid and codon MSAs. We show that a direct contact is more likely to be present when the correlation between the positions is strong at the amino acid level but weak at the codon level. The performance of different methods for analysing correlated mutations in predicting contacts is shown to be enhanced significantly when amino acid and codon data are combined.
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spelling doaj.art-20fcd743a0f543a08d542531d80e4c862022-12-22T04:32:42ZengeLife Sciences Publications LtdeLife2050-084X2015-09-01410.7554/eLife.08932Codon-level information improves predictions of inter-residue contacts in proteins by correlated mutation analysisEtai Jacob0Ron Unger1Amnon Horovitz2The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel; Department of Structural Biology, Weizmann Institute of Science, Rehovot, IsraelThe Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, IsraelDepartment of Structural Biology, Weizmann Institute of Science, Rehovot, IsraelMethods for analysing correlated mutations in proteins are becoming an increasingly powerful tool for predicting contacts within and between proteins. Nevertheless, limitations remain due to the requirement for large multiple sequence alignments (MSA) and the fact that, in general, only the relatively small number of top-ranking predictions are reliable. To date, methods for analysing correlated mutations have relied exclusively on amino acid MSAs as inputs. Here, we describe a new approach for analysing correlated mutations that is based on combined analysis of amino acid and codon MSAs. We show that a direct contact is more likely to be present when the correlation between the positions is strong at the amino acid level but weak at the codon level. The performance of different methods for analysing correlated mutations in predicting contacts is shown to be enhanced significantly when amino acid and codon data are combined.https://elifesciences.org/articles/08932protein evolutioncorrelated mutationsstructure prediction
spellingShingle Etai Jacob
Ron Unger
Amnon Horovitz
Codon-level information improves predictions of inter-residue contacts in proteins by correlated mutation analysis
eLife
protein evolution
correlated mutations
structure prediction
title Codon-level information improves predictions of inter-residue contacts in proteins by correlated mutation analysis
title_full Codon-level information improves predictions of inter-residue contacts in proteins by correlated mutation analysis
title_fullStr Codon-level information improves predictions of inter-residue contacts in proteins by correlated mutation analysis
title_full_unstemmed Codon-level information improves predictions of inter-residue contacts in proteins by correlated mutation analysis
title_short Codon-level information improves predictions of inter-residue contacts in proteins by correlated mutation analysis
title_sort codon level information improves predictions of inter residue contacts in proteins by correlated mutation analysis
topic protein evolution
correlated mutations
structure prediction
url https://elifesciences.org/articles/08932
work_keys_str_mv AT etaijacob codonlevelinformationimprovespredictionsofinterresiduecontactsinproteinsbycorrelatedmutationanalysis
AT ronunger codonlevelinformationimprovespredictionsofinterresiduecontactsinproteinsbycorrelatedmutationanalysis
AT amnonhorovitz codonlevelinformationimprovespredictionsofinterresiduecontactsinproteinsbycorrelatedmutationanalysis