Simulations of Biomolecular Fragmentation and Diffraction with Ultrafast X-ray Lasers

Abstract: Studies of biomolecules have recently seen substantial developments. New X-ray lasers allow for high-resolution imaging of protein crystals too small for conventional X-ray crystallography. Even structures of single particles have been determined at lower resolutions with these new sources. The secret lies in the ultrashort high-intensity pulses, which allow for diffraction and retrieval of structural information before the sample gets fragmented. However, the attainable resolution is still limited, in particular when imaging non-crystalline samples, making further advancements highly desired. In this thesis, some of the resolution-limiting obstacles facing single particle imaging (SPI) of proteins are studied in silico.As the X-ray pulse interacts with injected single molecules, their spatial orientation is generally unknown. Recovering the orientation is essential to the structure determination process, and currently nontrivial. Molecular dynamics simulations show that the Coulomb explosion due to intense X-ray ionization could provide information pertaining to the original orientation. Used in conjunction with current methods, this would lead to an enhanced three-dimensional reconstruction of the protein.Radiation damage and sample heterogeneity constitute considerable sources of noise in SPI. Pulse durations are presently not brief enough to circumvent damage, causing the sample to deteriorate during imaging, and the accuracy of the averaged diffraction pattern is impaired by structural variations. The extent of these effects were studied by molecular dynamics. Our findings suggest that radiation damage in terms of ionization and atomic displacement promotes a gating mechanism, benefiting imaging with longer pulses. Because of this, sample heterogeneity poses a greater challenge and efforts should be made to minimize its impact.X-ray lasers generate pulses with a stochastic temporal distribution of photons, affecting the achievable resolution on a  pulse-to-pulse basis. Plasma simulations were performed to investigate how these fluctuations influence the damage dynamics and the diffraction signal. The results reveal that structural information is particularly well-preserved if the temporal distribution is skewed such that most photons are concentrated at the beginning.While many obstacles remain, the prospect of atomic-resolution SPI is drawing ever closer. This thesis is but one of the stepping stones necessary to get us there. Once we do, the possibilities are limitless.