R-CCS Cafe第252回（2023年9月15日）

Title:
Automated Density Extraction of Isomorphous Difference map and Occupancy-estimation for Conformer Fitting
Abstract:
TR-SFX (Time-Resolved Serial Femtosecond Crystallography) is a powerful technique that enables the capture and analysis of time-evolved dynamics of residual motion across various crystal structures, thereby facilitating the visual inspection of reaction kinetics. A critical step in elucidating intermittent reaction states involves the analysis of the isomorphous difference map, which provides valuable information about the variations in atomic positions between different crystal structures.

In this study, a clustering-based methodology was employed to cluster difference electron densities and establish associations with adjacent residues. Singular Value Decomposition (SVD) techniques were additionally utilized to identify and rank residues exhibiting motion, quantified by their electron density sum. Moreover, a network representation was further employed to highlight connections between these mobile residues in protein. Our tool not only identifies important residues linked to reaction kinetics, but also employs structure factor extrapolation techniques to compute the occupancy of structural intermediates. Following the identification of the residues having significant difference density, we extracted their conformers from molecular dynamics trajectory. These extracted conformers were then subjected to refinement, enhancing conformational sampling space for generating triggered state structure validated by real space correlation coefficient.

Our approach significantly enhances the structural characterization process providing a deeper understanding of the dynamic behavior and reaction mechanisms within crystal structures. Through the combination of TR-SFX with molecular dynamics-based fitting, we enable more accurate and detailed investigations of reaction kinetics and structural changes.
This has wider implications in fields such as materials science, drug discovery, and catalysis, paving the way for transformative discoveries and applications.