Structure ensemble prediction methods are unable to accurately model subtle conformational differences captured by X-ray crystallography

Summary

Protein structural ensemble prediction methods such as AlphaFlow and ESMFlow, as well as MSA-based tricks such as subsampling and clustering, are unable to capture alternate conformations found in X-ray-crystallography density (1). In contrast, MD simulations can often (but not always) sample both states.

Figures

Ref (1)

See also

• X-ray density can capture alternate conformations of proteins and their ligands

1.

Rosenberg AA, Vedula S, Bronstein AM, Marx A. Seeing Double: Molecular dynamics simulations reveal the stability of certain alternate protein conformations in crystal structures. openRxiv; 2024. Available from: https://doi.org/10.1101/2024.08.31.610605