Learning Dynamic Protein Representations at Scale with Distograms

Nicolas Portal, Wissam Karroucha, Vincent Mallet, Massimiliano Bonomi

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Track: long paper (4–8 pages excluding references)

Keywords: Representation learning, Protein structure, Dynamics

Abstract: Protein function and other biological properties often depend on structural dynamics, yet most machine-learning predictors rely on static representations. Physics-based molecular simulations can describe conformational variability but remain computationally prohibitive at scale. Generative models provide a more efficient alternative, though their ability to produce accurate conformational ensembles is still limited. In this work, we bypass expensive simulations by leveraging residue–residue distance probability distributions (distograms) from structure predictors such as AlphaFold2. Our approach provides a scalable way to encode dynamic information into protein representations, aiming to improve function prediction without explicit conformational sampling.

Anonymization: This submission has been anonymized for double-blind review via the removal of identifying information such as names, affiliations, and identifying URLs.

Submission Number: 35