Capturing coevolutionary signals in repeat proteins

TL;DR

This paper develops a statistical method to detect true co-evolutionary signals in repeat proteins by correcting biases caused by their translational symmetry, enabling better identification of native contacts.

Contribution

It introduces a bias correction technique for statistical coupling analysis in repeat proteins, improving the detection of genuine co-evolutionary signals.

Findings

Bias correction reveals true co-evolutionary signals

Method identifies native contacts in repeat proteins

Minimum sequence number needed for reliable analysis

Abstract

The analysis of correlations of amino acid occurrences in globular proteins has led to the development of statistical tools that can identify native contacts -- portions of the chains that come to close distance in folded structural ensembles. Here we introduce a statistical coupling analysis for repeat proteins -- natural systems for which the identification of domains remains challenging. We show that the inherent translational symmetry of repeat protein sequences introduces a strong bias in the pair correlations at precisely the length scale of the repeat-unit. Equalizing for this bias reveals true co-evolutionary signals from which local native-contacts can be identified. Importantly, parameter values obtained for all other interactions are not significantly affected by the equalization. We quantify the robustness of the procedure and assign confidence levels to the interactions, identifying the minimum number of sequences needed to extract evolutionary information in several repeat protein families. The overall procedure can be used to reconstruct the interactions at long distances, identifying the characteristics of the strongest couplings in each family, and can be applied to any system that appears translationally symmetric.