Representation choice shapes the interpretation of protein conformational dynamics

Fuente: arXiv
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Autores principales: Giottonini, Axel, Lemmin, Thomas
Formato: Preprint
Publicado: 2026
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author Giottonini, Axel
Lemmin, Thomas
author_facet Giottonini, Axel
Lemmin, Thomas
contents Molecular dynamics simulations provide detailed trajectories at the atomic level, but extracting interpretable and robust insights from these high-dimensional data remains challenging. In practice, analyses typically rely on a single representation. Here, we show that representation choice is not neutral: it fundamentally shapes the conformational organization, similarity relationships, and apparent transitions inferred from identical simulation data. To complement existing representations, we introduce Orientation features, a geometrically grounded, rotation-aware encoding of protein backbone. We compare it against common descriptions across three dynamical regimes: fast-folding proteins, large-scale domain motions, and protein-protein association. Across these systems, we find that different representations emphasize complementary aspects of conformational space, and that no single representation provides a complete picture of the underlying dynamics. To facilitate systematic comparison, we developed ManiProt, a library for efficient computation and analysis of multiple protein representations. Our results motivate a comparative, representation-aware framework for the interpretation of molecular dynamics simulations.
format Preprint
id arxiv_https___arxiv_org_abs_2604_00580
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Representation choice shapes the interpretation of protein conformational dynamics
Giottonini, Axel
Lemmin, Thomas
Machine Learning
Biomolecules
Molecular dynamics simulations provide detailed trajectories at the atomic level, but extracting interpretable and robust insights from these high-dimensional data remains challenging. In practice, analyses typically rely on a single representation. Here, we show that representation choice is not neutral: it fundamentally shapes the conformational organization, similarity relationships, and apparent transitions inferred from identical simulation data. To complement existing representations, we introduce Orientation features, a geometrically grounded, rotation-aware encoding of protein backbone. We compare it against common descriptions across three dynamical regimes: fast-folding proteins, large-scale domain motions, and protein-protein association. Across these systems, we find that different representations emphasize complementary aspects of conformational space, and that no single representation provides a complete picture of the underlying dynamics. To facilitate systematic comparison, we developed ManiProt, a library for efficient computation and analysis of multiple protein representations. Our results motivate a comparative, representation-aware framework for the interpretation of molecular dynamics simulations.
title Representation choice shapes the interpretation of protein conformational dynamics
topic Machine Learning
Biomolecules
url https://arxiv.org/abs/2604.00580