Representation choice shapes the interpretation of protein conformational dynamics

arXiv:2604.00580v1 Announce Type: cross
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.