2026/03/02 by Advaith Maddipatla, Sanketh Vedula, Alex Bronstein +1 · 1 voice
Materials Science · Biochemistry, Genetics and Molecular Biology · #Enzyme Structure and Function #Protein Structure and Dynamics #Connective tissue disorders research
paper · doi:10.64898/2026.02.27.708490
openalex publication_date 2026/03/02 · openalex created_date 2026/03/03 · openalex updated_date 2026/07/14
Abstract Although X-ray crystallography captures the ensemble of conformations present within the crystal lattice, models typically depict only the most dominant conformation, obscuring the existence of alternative states. Applying the electron density-guided AlphaFold3 approach to β 2 -Microglobulin highlights how ensembles of alternate backbone conformations can be systematically modeled directly from crystallographic maps. This study also highlights how the detection of conformational ensembles is affected by the local quality of electron density and subtle variations in crystallization conditions and lattice packing. These results demonstrate that density-guided AlphaFold3 can uncover conformational heterogeneity missed by conventional refinement, offering a robust, systematic framework to capture the full structural landscape of proteins in crystals and enhancing the interpretive power of macromolecular crystallography. Synopsis Electron-density-guided AlphaFold3 reveals previously unmodeled conformational heterogeneity in β 2 -Microglobulin and shows how crystal packing influences ensemble detection in X-ray crystallography.