Prof. Gunnar F. Schroder
Computational Structural Biology Group
Institute of Complex Systems (ICS-6)
Forschungszentrum Julich, Germany

Monday, September 23, 2013
3:00 pm (CT)
3269 Beckman Institute

Abstract

Single-particle cryo-EM has become a powerful technique to determine the structure of large proteins. We are developing computational tools to build and refine protein models into cryo- EM density maps. With recent technical advances a resolution of 4 Å is now reachable. An approach will be presented to build protein backbone traces into intermediate- and low- resolution cryo-EM density maps. To build accurate protein models from low-resolution data requires to refine protein structures and predict local structural details that are not resolved by the experiment. Our approach is based on restrained MD simulations and it is shown how the use of evolutionary information can significantly improve the refinement. Single-particle Cryo-EM offers, at least in principle, access to the distribution of conformations, i.e. the conformational variance. However, due to a low signal-to-noise ratio of the images this distribution is very difficult to determine. In the talk, I will show how functionally relevant conformational dynamics can be extracted from single-particle data.