Representation choice shapes the interpretation of protein conformational dynamics

• URL: http://arxiv.org/abs/2604.00580v1
• Date: Wed, 01 Apr 2026 07:38:52 GMT
• Title: Representation choice shapes the interpretation of protein conformational dynamics
• Abstract summary: We show that representation choice is not neutral and shapes the organization, similarity relationships, and apparent transitions inferred from identical simulation data.<n>To complement existing representations, we introduce Orientation features, a geometrically grounded, rotation-aware encoding of protein backbone.<n>We find that different representations emphasize complementary aspects of conformational space, and that no single representation provides a complete picture of the underlying dynamics.
• Score: 0.0
• License: http://creativecommons.org/licenses/by/4.0/
• Abstract: 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.

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