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Title page for ETD etd-02252011-123124

Type of Document Dissertation
Author Lindert, Steffen
URN etd-02252011-123124
Title Cryo-EM guided de novo protein folding
Degree PhD
Department Chemical and Physical Biology
Advisory Committee
Advisor Name Title
Al Beth Committee Chair
Charles Sanders Committee Member
Michael Stone Committee Member
Phoebe Stewart Committee Member
  • hybrid methods
  • de novo protein folding
  • cryoEM
Date of Defense 2010-11-22
Availability unrestricted
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.
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