Deciphering continuous MOLecular MOVements of BIOmacromolecular complexes by new cryo-Electron Microscopy image analysis methods – EMBioMolMov

Cryo-electron microscopy (cryo-EM) is under constant development for a routine determination of biomolecular structures (conformations) at high resolution. This project is focused on the development of approaches for identifying continuous conformational transitions from cryo-EM images through high-resolution determination of the entire conformational variability of studied complexes. We have established the basis for one such approach by combining image analysis with molecular mechanics simulations. To obtain high-resolution information regarding the full conformational variability, three simulation methods will be studied in combination with image analysis and artificial intelligence methods. The new approaches will be useful for studying a large range of biomacromolecular complexes in the field of structural biology. Synthetic cryo-EM data of various complexes will be used to validate and compare these approaches. The best-performing approach will be valorized using experimental cryo-EM data of two biomedically important complexes (human 80S ribosome and human p97 AAA ATPase).