Sequence correlations shape protein promiscuity

TL;DR

This paper analytically demonstrates that diagonal correlations in protein sequences increase their likelihood of nonspecific binding, explaining observed sequence patterns and suggesting experimental validation.

Contribution

It provides a theoretical explanation linking sequence correlations to protein promiscuity, supported by analytical predictions and biological observations.

Findings

Diagonal correlations enhance nonspecific binding propensity.

Sequence repeats are statistically significant in promiscuous proteins.

Analytical robustness across interaction models and compositions.

Abstract

We predict analytically that diagonal correlations of amino acid positions within protein sequences statistically enhance protein propensity for nonspecific binding. We use the term 'promiscuity' to describe such nonspecific binding. Diagonal correlations represent statistically significant repeats of sequence patterns where amino acids of the same type are clustered together. The predicted effect is qualitatively robust with respect to the form of the microscopic interaction potentials and the average amino acid composition. Our analytical results provide an explanation for the enhanced diagonal correlations observed in hubs of eukaryotic organismal proteomes [J. Mol. Biol. 409, 439 (2011)]. We suggest experiments that will allow direct testing of the predicted effect.