Cryo-EM guided de novo protein folding

Abstract

In the course of this dissertation a software EM-Fold was developed that combines de-novo protein structure prediction and medium resolution cryoEM density maps. It can be applied to proteins containing α-helices and β-strands if the density map has sufficient resolution to observe these secondary structure elements. EM-Fold was proven to be reliable over a large range of protein sizes in several benchmarks on simulated and experimental density maps. The software was used to predict a model for one of the capsid proteins of human Adenovirus, protein IIIa, for which there was no crystal structure available. EM-Fold in combination with Rosetta was be able to recover atomic detail information in several benchmark cases. A separate line of research dealt with the determination of a medium resolution density map of the Adenovirus-Integrin complex. The density was able to corroborate the extension model for integrin binding to a multivalent RGD ligand.