Serial X-ray crystallography : pushing the boundaries of structure and dynamics
Abstract/Contents
- Abstract
- Over its long history, macromolecular X-ray crystallography has proven to be the most popular method for structural biology. Recent advent of serial X-ray crystallography at X-ray free-electron laser facilities and synchrotrons have revolutionized the field allowing scientists to study proteins that were previously inaccessible. Radiation damage-free structures from microcrystals at room temperature are routinely studied these days. The next frontier of serial X-ray crystallography will be in studying the function of the proteins by reconstructing a detailed movie of the protein in motion. Conformational variations/changes of proteins are studied using diffuse scattering and pump-probe type of experiments. My research is focused on developing advanced data analysis methods in the field of macromolecular X-ray crystallography to extract more information from massive datasets and push the boundaries of the status quo. Here is a summary of projects I would like to highlight. The first project advances the analysis of pump-probe and mixing-jet experiments by applying machine learning to correct for uncertainty/inaccuracy of measured pumping or mixing times in serial femtosecond X-ray crystallography (SFX) experiments. In pump-probe or mixing-jet experiments, we either excite the crystals using an optical light or mix the crystals with a catalyst to trigger motion, followed by an X-ray probe after a certain delay. Although these methods have been broadly used to study protein dynamics, few people have considered the effects of jitter in these inaccurate timestamps, which can be critical in the study of ultrafast protein dynamics. In our work, we have applied the diffusion map method to embed high-dimensional diffraction images into low-dimensional latent space to correct for the time jitter. The second project is a reproducibility study of diffuse scattering in crystalline isocyanide hydratase in three forms, its wild type and two mutants. Different from ultrabright Bragg peaks that arise from the coherent diffraction of periodic crystal lattices, diffuse scattering is much weaker and is induced by imperfections inside the crystal lattice, such as protein motion and/or other forms of disorders. I have developed advanced methods to extract much weaker diffuse scattering signals from diffraction images, and then studied possible protein motions that cause these diffuse signals, by comparing liquid-like motions model to the experimental data. This work demonstrates a potential utility for selecting a preferred atomic displacement parameter model from diffuse scattering data.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Su, Zhen |
|---|---|
| Degree supervisor | Dunne, Anthony Michael |
| Degree supervisor | Reis, David A, 1970- |
| Thesis advisor | Dunne, Anthony Michael |
| Thesis advisor | Reis, David A, 1970- |
| Thesis advisor | Hedman, B. (Britt), 1949- |
| Degree committee member | Hedman, B. (Britt), 1949- |
| Associated with | Stanford University, Department of Applied Physics |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Zhen Su. |
|---|---|
| Note | Submitted to the Department of Applied Physics. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/zn608xn7063 |
Access conditions
- Copyright
- © 2022 by Zhen Su
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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