Scaling and merging time-resolved pink-beam diffraction with variational inference
Category
Published on
Type
journal-article
Author
Kara A. Zielinski and Cole Dolamore and Harrison K. Wang and Robert W. Henning and Mark A. Wilson and Lois Pollack and Vukica Srajer and Doeke R. Hekstra and Kevin M. Dalton
Citation
Zielinski, K. A., Dolamore, C., Wang, H. K., Henning, R. W., Wilson, M. A., Pollack, L., Srajer, V., Hekstra, D. R., & Dalton, K. M. (2024). Scaling and merging time-resolved pink-beam diffraction with variational inference. Structural Dynamics, 11(6). https://doi.org/10.1063/4.0000269
Abstract
Time-resolved x-ray crystallography (TR-X) at synchrotrons and free electron lasers is a promising technique for recording dynamics of molecules at atomic resolution. While experimental methods for TR-X have proliferated and matured, data analysis is often difficult. Extracting small, time-dependent changes in signal is frequently a bottleneck for practitioners. Recent work demonstrated this challenge can be addressed when merging redundant observations by a statistical technique known as variational inference (VI). However, the variational approach to time-resolved data analysis requires identification of successful hyperparameters in order to optimally extract signal. In this case study, we present a successful application of VI to time-resolved changes in an enzyme, DJ-1, upon mixing with a substrate molecule, methylglyoxal. We present a strategy to extract high signal-to-noise changes in electron density from these data. Furthermore, we conduct an ablation study, in which we systematically remove one hyperparameter at a time to demonstrate the impact of each hyperparameter choice on the success of our model. We expect this case study will serve as a practical example for how others may deploy VI in order to analyze their time-resolved diffraction data.
