Next Generation Integrative Modeling for Cryo-Electron Microscopy

Supervisors: Prof. Michael Kolbe (HZI, UHH), Prof. Matthias Rarey (UHH)

Cryo-electron microscopy (cryo-EM) is an emerging technology in the field of structural biology. Especially for larger biomolecular assemblies (hundreds of kDa to MDa) it is becoming the method of choice and might play a crucial role in the understanding of cellular processes at the molecular level. Although cryo-EM structures with near to atomic resolution exist, the most frequent scenario is models at slightly lower resolutions of 4-8 Å. Moreover, the resolution can vary considerably for different volumes of a given cryo-EM map which makes structural interpretation sometimes challenging. To overcome the information gap, various different data sources are usually combined into an integrative modelling approach. Highly sophisticated computational techniques combining spatial pattern recognition with precise molecular modelling are required to create overall models with atomic resolution. The project focuses on two challenging problems that researchers often face when working with EM. We want to develop better tools for the interpretation of mid resolution electron density maps by integrating atomic structures from other biophysical methods under consideration of conformational flexibility. Second, we want to improve the detection of self-similarity and local symmetry in density maps and consider this information upon model building.