Biological samples are highly radiation sensitive. The rapid progress of their radiation damage prevents accurate structure determination of single macromolecular assemblies in standard diffraction experiments. However, computer simulations of the damage formation have shown that the radiation tolerance might be extended at very high intensities with ultrafast imaging such as is possible with the presently developed and operating x-ray free-electron lasers. Recent experiments with free-electron lasers on nanocrystals have demonstrated proof of the imaging principle at resolutions down to 1:6 Angstroms. However, there are still many physical and technical problems to be clarified on the way to imaging of single biomolecules at atomic resolution. In particular, theoretical simulations try to address an important question: How does the radiation damage progressing within an imaged single object limit the structural information about this object recorded in its diffraction image during a 3D imaging experiment? This information is crucial for adjusting pulse parameters during imaging so that high-resolution diffraction patterns can be obtained. Further, dynamics simulations should be used to verify the accuracy of the structure reconstruction performed from the experimental data. This is an important issue as the experimentally recorded diffraction signal is recorded from radiation-damaged samples. It also contains various kinds of background. In contrast, the currently used reconstruction algorithms assume perfectly coherent scattering patterns with shot noise only. In this review paper, we discuss the most important processes and effects relevant for imaging-related simulations that are not yet fully understood, or omitted in the irradiation description. We give estimates for their contribution to the overall radiation damage. In this way we can identify unsolved issues and challenges for simulations of x-ray irradiated single molecules relevant for imaging studies. They should be addressed during further development of these simulation tools.

In this work, we analyze the application of X-ray diffraction imaging techniques to follow ultrafast structural transitions in solid materials using the example of an X-ray pump–X-ray probe experiment with a single-crystal silicon performed at a Linac Coherent Light Source. Due to the spatially non-uniform profile of the X-ray beam, the diffractive signal recorded in this experiment included contributions from crystal parts experiencing different fluences from the peak fluence down to zero. With our theoretical model, we could identify specific processes contributing to the silicon melting in those crystal regions, i.e., the non-thermal and thermal melting whose occurrences depended on the locally absorbed X-ray doses. We then constructed the total volume-integrated signal by summing up the coherent signal contributions (amplitudes) from the various crystal regions and found that this significantly differed from the signals obtained for a few selected uniform fluence values, including the peak fluence. This shows that the diffraction imaging signal obtained for a structurally damaged material after an impact of a non-uniform X-ray pump pulse cannot be always interpreted as the material’s response to a pulse of a specific (e.g., peak) fluence as it is sometimes believed. This observation has to be taken into account in planning and interpreting future experiments investigating structural changes in materials with X-ray diffraction imaging.

In this work, we report on incorporating for the first time tree-algorithm based solvers into the molecular dynamics code, XMDYN. XMDYN was developed to describe the interaction of ultrafast X-ray pulses with atomic assemblies. It is also a part of the simulation platform, SIMEX, developed for computational single-particle imaging studies at the SPB/SFX instrument of the European XFEL facility. In order to improve the XMDYN performance, we incorporated the existing tree-algorithm based Coulomb solver, PEPC, into the code, and developed a dedicated tree-algorithm based secondary ionization solver, now also included in the XMDYN code. These extensions enable computationally efficient simulations of X-ray irradiated large atomic assemblies, e.g., large protein systems or viruses that are of strong interest for ultrafast X-ray science. The XMDYN-based preparatory simulations can now guide future single-particle-imaging experiments at the free-electron-laser facility, EuXFEL.

We investigate the radiation damage dynamics of nanocrystals at high x-ray intensity, by using time-resolved scattering patterns. We present dynamics simulations for biologically relevant molecules using XMDYN extended to nanocrystals and scattering simulation with XSINC.