Flexible fitting method translates high-speed atomic force microscopy images into precise protein motion models

High-speed atomic force microscopy (HS-AFM) is the only experimental technique to directly watch proteins in dynamic action. However, as a surface scanning technique with limited spatial resolution, HS-AFM will inevitably provide insufficient information for detailed atomistic understanding of biomolecular function. Despite previous efforts in computational modeling attempting to overcome such limitations, successful applications to retrieve atomistic-level information from measurements are practically absent.