Enrollment and place of work: Uppsala University

PhD Project 6

Photon-matter interaction: Orientation from Coulomb explosion

Enrolment in Doctoral degree: Uppsala University, Uppsala, Sweden

Place of work: Dept of Physics & Astronomy, Uppsala University, Uppsala, Sweden

Supervisor: Prof. Dr. Carl Caleman, Dr. Erik Marklund, Prof. Dr. Sadia Bari

Single particle imaging  using X-ray pulses has become increasingly attainable with the advent of high-intensity free electron lasers. Eliminating the need for crystallised samples enables structural studies of molecules previously inaccessible by conventional crystallography. While this emerging technique already demonstrates substantial promise, some obstacles need to be overcome before SPI can reach its full potential. One such problem is determining the spatial orientation of the sample at the time of X-ray interaction. Simulations have predicted that the orientation of the protein at the instant when it is exposed to the X-ray pulse, can be determined by mapping the distribution of the ejected ions as the sample undergoes a Coulomb explosion following the intense ionisation. By detecting the ions ejected from the fragmented sample, the orientation of the original sample should be possible to determine. Knowledge of the orientation has been shown earlier to be of substantial advantage in the reconstruction of the original structure. This idea has potential to develop into a crucial tool for orientation retrievement in SPI experiments, but for it to reach its full potential we need to do further studies, both experimentally and using simulations. This project focuses on the simulations, with the goal to answer questions such as:  “What is the dependence between the reproducibility of the ion distribution maps and the structure of the protein?”,  “How well do we need to determine the orientation for the orientation algorithms to benefit?” These questions will be addressed by combining results from atomic simulation and machine learning algorithms, and tested with experiments. This project includes additional secondments within the SPIDocs consortium at DESY in Hamburg.

PhD Project 7

Field orientation theory

Enrolment in Doctoral degree: Uppsala University, Uppsala, Sweden

Place of work: Dept of Chemistry – BMC, Uppsala University, Uppsala, Sweden

Supervisor: Dr. Erik Marklund, Prof. Dr. Carl Caleman

It has been shown that strong electric fields can be used to orient proteins. The limits of how this phenomenon can be implemented and how far it can be used to support X-ray molecular imaging is currently unknown however. This PhD project takes place on the cusp between biochemistry and biophysics, and aims to investigate how field orientation can be used to study protein structure; provide better understanding of the damping effects; answer how much orientation is enough for it to be of utility for structure determination; understand the transfer of molecules into the gas phase by refining the physical models used for simulation on the basis of recent and emerging knowledge about the electrospray process. These points will be addressed using computer simulations in collaboration with experimentalists in native mass spectrometry, ion mobility spectrometry, and other relevant fields. Classical molecular dynamics methods will be central for this project, which may be complemented with other levels of physical computations and machine learning approaches. This project will be carried out in the Biochemistry programme at the Dept of Chemistry – BMC, and includes additional secondments within the SPIDocs consortium at IMIC and MS Vision.

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