Out-of-equilibrium selection pressure enhances inference from protein sequence data

2026/02/11 by Nicola Dietler, Cyril Malbranke, Anne-Florence Bitbol · 1 voice
Biochemistry, Genetics and Molecular Biology · #q-bio.BM

paper · pdf · doi:10.1101/2025.05.14.654088

Abstract

Homologous proteins have similar three-dimensional structures and biological functions that shape their sequences. The resulting coevolution-driven correlations underlie methods from Potts models to AlphaFold, which infer protein structure and function from sequences. Using a minimal model, we show that fluctuating selection strength and the onset of new selection pressures improve coevolution-based inference of structural contacts. Our conclusions extend to realistic synthetic data and to the inference of interaction partners. Out-of-equilibrium noise arising from ubiquitous variations in natural selection thus enhances, rather than hinders, the success of inference from protein sequences.

Citations

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Discussions

• Nicola Dietler, Cyril Malbranke, Anne-Florence Bitbol: Out-of-equilibrium selection pressure enhances inference from protein sequence data https://arxiv.org/abs/2602.11427 https://arxiv.org/pdf/2602.1 [bsky, 0 points, 0 comments]

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