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

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Abstract

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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Etai Jacob

The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel

Competing interests
The authors declare that no competing interests exist.
Ron Unger

The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel

Competing interests
The authors declare that no competing interests exist.
Amnon Horovitz

Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel

For correspondence
Amnon.Horovitz@weizmann.ac.il

Competing interests
The authors declare that no competing interests exist.

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