Macromolecular Dynamics by Hybrid Electron Microscopy Normal Mode Analysis

Structural changes are critical for biological functions of proteins and describing conformational changes in large macromolecular complexes is a major challenge. To allow full studies of gradual conformational changes, we have recently developed Hybrid Electron Microscopy Normal Mode Analysis (HEMNMA) [1]. HEMNMA uses normal modes to elastically align electron microscopy (EM) images with a reference structure, in order to determine the conformations present in images and evaluate their pertinence. HEMNMA allows analyzing gradual changes more extensively than other EM methods, as HEMNMA gives full dynamics while other EM methods give only a few conformations. The computed conformational distribution allows modeling of transition pathways. Here, we show the performance of HEMNMA using simulated data (Fig. 1). The results of the method with experimental EM images will be shown at the symposium. Also, we will show a user-friendly graphical interface to the method that we have recently built within the Xmipp software.