dc.contributor.advisor | Grubmüller, Helmut Prof. Dr. | |
dc.contributor.author | von Ardenne, Benjamin | |
dc.date.accessioned | 2018-06-18T08:40:53Z | |
dc.date.available | 2018-06-18T08:40:53Z | |
dc.date.issued | 2018-06-18 | |
dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-002E-E424-4 | |
dc.identifier.uri | http://dx.doi.org/10.53846/goediss-6928 | |
dc.language.iso | eng | de |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject.ddc | 530 | de |
dc.title | Structure Determination From Single Molecule X-Ray Scattering Experiments using Photon Correlations | de |
dc.type | doctoralThesis | de |
dc.contributor.referee | Müller, Marcus Prof. Dr. | |
dc.date.examination | 2017-10-18 | |
dc.subject.gok | Physik (PPN621336750) | de |
dc.description.abstracteng | Scattering experiments with femtosecond high-intensity free-electron laser pulses
provide a new route to macromolecular structure determination without the need
for crystallization at low material usage. In these experiments, the X-ray pulses
are scattered with high repitition on a stream of identical single biomolecules and
the scattered photons are recorded on a pixelized detector. The main challenges
in these experiments are the unknown random orientation of the molecule in each
shot and the extremely low signal to noise ratio due to the very low expected
photon count per scattering image, typically well below the number of over 100
photons required by available analysis methods. The latter currently limits the
scattering experiments to nano-crystals or larger virus particles, but the ultimate
goal remains to retrieve the atomic structure of single biomolecules.
In light of that goal, here I present a correlation-based approach that can determine
the molecular structure de novo from as few as three coherently scattered
photons per image. I derive for the first time an analytic expression of the full
three-photon correlation as a function of the molecules Fourier intensity using a
spherical harmonics expansion and propose a Monte Carlo simulated annealing
approach to solve the inverse problem of finding an intensity that fits the experimentally
observed triple correlations. The size of the search space is reduced by
using information from the analytic inversion of the two-photon correlation and
the electron density is retrieved by applying an iterative phase retrieval method
to the determined intensity.
Using synthetic scattering data of a small protein (46 residues) at realistic average
photons counts of 10 photons per image, I demonstrate that near-atomic
resolution of 3.3 Å can be achieved using 3.3 · 10<sup>9</sup> images, which is within experimental
reach. Remarkably, the data acquisition time required to achieve the
same resolution decreases to minutes if the average number of photons per image
is increased to only 100 photons (equivalent to a decrease in the number of images
by a factor 1000).
The noise levels in the experiment are expected to be quite high which is a challenge
for all structure determination methods. To address this issue, I demonstrate
that my three-photon correlation approach is robust to isotropic noise from incoherent
scattering, and that the number of disordered solvent molecules attached
to the macromolecular surface should be kept at a minimum. | de |
dc.contributor.coReferee | Stark, Holger Prof. Dr. | |
dc.subject.eng | structure determination xfel single molecule photon correlations | de |
dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-002E-E424-4-2 | |
dc.affiliation.institute | Fakultät für Physik | de |
dc.identifier.ppn | 1024706532 | |