Simulation atomic force microscopy to predict correlated conformational dynamics in proteins from topographic imaging

Abstract

Atomic force microscopy (AFM) of proteins can detect only changes within the scanned molecular surface, missing all motions in other regions and thus information about functionally relevant conformational couplings. We show that simulation AFM can overcome this drawback by reconstruction of 3D molecular structures from topographic AFM images. A proof of principle demonstration is provided for an in-silico AFM experiment visualizing the conformational dynamics of a membrane transporter. The application shows that the alternating access mechanism underlying its operation can be retrieved from only AFM imaging of one membrane side. Simulation AFM is implemented in the freely available BioAFMviewer software platform, providing the convenient applicability to better understand experimental AFM observations.