2024/04/15 by Eugene Klyshko, Justin Sung-Ho Kim, Lauren McGough +4 · 1 voice · 3 citations
Biochemistry, Genetics and Molecular Biology · Materials Science · Physics and Astronomy · #Enzyme Structure and Function #Force Microscopy Techniques and Applications #Protein Structure and Dynamics
paper · pdf · doi:10.1038/s41467-024-47473-4
openalex publication_date 2024/04/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
Proteins are molecular machines and to understand how they work, we need to understand how they move. New pump-probe time-resolved X-ray diffraction methods open up ways to initiate and observe protein motions with atomistic detail in crystals on biologically relevant timescales. However, practical limitations of these experiments demands parallel development of effective molecular dynamics approaches to accelerate progress and extract meaning. Here, we establish robust and accurate methods for simulating dynamics in protein crystals, a nontrivial process requiring careful attention to equilibration, environmental composition, and choice of force fields. With more than seven milliseconds of sampling of a single chain, we identify critical factors controlling agreement between simulation and experiments and show that simulated motions recapitulate ligand-induced conformational changes. This work enables a virtuous cycle between simulation and experiments for visualizing and understanding the basic functional motions of proteins.