Speaker
Description
The ability of single-particle cryo-EM to furnish hundreds of thousand images of molecules fast-frozen in solution means that even rarely sighted conformations, corresponding to high-energy states, are represented in the data set. As a consequence, a continuum of states is experimentally accessible (Frank, Biochemistry 2018). Current practice of cryo-EM structure research does not take advantage of this opportunity. In collaboration with Abbas Ourmazd and Peter Schwander at the University of Wisconsin in Milwaukee we have developed an approach to map this continuum into a low-dimensional space by employing manifold embedding (Dashti et al., PNAS 2014; bioarxiv 2018; biorxiv 2019). From the observed occupancies the free energies of the molecule can be computed. The resulting free-energy landscape reveals the trajectories of states readily accessible by the molecule in the thermal bath, and the way the molecule's function is encoded in these trajectories. A Python implementation of this software, ManifoldEM, is being prepared for distribution.
