dc.contributor.advisor | Stark, Holger Prof. Dr. | |
dc.contributor.author | Lambrecht, Felix | |
dc.date.accessioned | 2019-02-20T14:55:46Z | |
dc.date.available | 2019-02-20T14:55:46Z | |
dc.date.issued | 2019-02-20 | |
dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-002E-E59E-A | |
dc.identifier.uri | http://dx.doi.org/10.53846/goediss-7296 | |
dc.language.iso | eng | de |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject.ddc | 571.4 | de |
dc.title | Computational methods for the structure determination of highly dynamic molecular machines by cryo-EM | de |
dc.type | doctoralThesis | de |
dc.contributor.referee | Grubmüller, Helmut Prof. Dr. | |
dc.date.examination | 2019-02-16 | |
dc.description.abstracteng | In the last couple of years, electron cryomicroscopy (cryo-EM) has gained of rising importance
in the field of structural biology and biophysics. Not only that the routinely
achievable resolution of the method has dramatically increased to routinely near-atomic
resolution. First and foremost the opportunity to resolve structures which where far
beyond the size limit for classical methods such as X-ray crystallography and NMR increased
the popularity. These features make cryo-EM also more and more interesting
for the pharmaceutical industry. However, certain challenges are being unresolved until
today. One of them is the usage of the full dynamical information cryo-EM experiments
bring with them. The other is the fact that classical transmission electron microscopy
(TEM) on biological samples still is limited by the radiation sensitivity and the low signal
in the images. This thesis will first present a new algorithm based on statistical methods
to decipher the conformational landscape of a macromolecular complex from cryo-EM
experiments. This information can be used to quantify biochemical phenomena like allostery
on the intramolecular level. Such analyses will be discussed to be useful in the
drug development pipeline and help to understand the physical foundations of the regulation
and function of macromolecular complexes. Secondly, a new imaging method based
on scanning TEM will be introduced. In the corresponding publication we evaluate this
method in its capability to resolve non-biological samples as well as biological macromolecues.
We show that the surrounding medium influences the imaging process in a way that
no compromise between the applied dose and the achievable signal can be found and it
will be discussed what implications can be drawn for new biological imaging modes in
general. | de |
dc.contributor.coReferee | Habeck, Michael Dr. | |
dc.contributor.thirdReferee | Tittmann, Kai Prof. Dr. | |
dc.contributor.thirdReferee | Adio, Sarah Dr. | |
dc.subject.eng | cryo-EM | de |
dc.subject.eng | Biophysics | de |
dc.subject.eng | iDPC | de |
dc.subject.eng | Energy Landscapes | de |
dc.subject.eng | Conformational Dynamics | de |
dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-002E-E59E-A-2 | |
dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
dc.subject.gokfull | Biologie (PPN619462639) | de |
dc.identifier.ppn | 1049539575 | |