The network of stabilizing contacts in proteins studied by coevolutionary data

TL;DR

This paper improves an inverse Ising-model approach to analyze coevolutionary data, revealing networks of stabilizing contacts in proteins that differ from contact networks, aiding understanding of protein stability.

Contribution

The study optimizes the inverse Ising-model algorithm to better calculate effective energies, validating it on models and real proteins, and analyzes the stabilizing contact networks in proteins.

Findings

Effective energies correlate with native conformations.

Stabilizing contact networks differ from contact networks.

Validated approach predicts mutation free energies.

Abstract

The primary structure of proteins, that is their sequence, represents one of the most abundant set of experimental data concerning biomolecules. The study of correlations in families of co--evolving proteins by means of an inverse Ising--model approach allows to obtain information on their native conformation. Following up on a recent development along this line, we optimize the algorithm to calculate effective energies between the residues, validating the approach both back-calculating interaction energies in a model system, and predicting the free energies associated to mutations in real systems. Making use of these effective energies, we study the networks of interactions which stabilizes the native conformation of some well--studied proteins, showing that it display different properties than the associated contact network.