ResiDEM: Analytical\nTool for Isomorphous Difference\nElectron Density Maps Utilizing Dynamic Residue Identification via\nDensity Clustering

Time-resolved serial femtosecond crystallography (TR-SFX)\nof biological\nmolecules captures the time-evolved dynamics of the residual motions\nacross crystal structures, enabling the visualization of structural\nchanges in response to chemical and physical stimuli to elucidate\nthe relationship between the structure and function of the system\nunder study. However, interpretations of residual motions can be complex\nto deconvolute because of various factors such as the system’s\nsize, temporal and spatial complexity, and allosteric behavior away\nfrom active sites. Relying solely on electron density map visualization\ncan also pose a challenge in differentiating between useful and irrelevant\ndata. In order to accurately identify residues and determine their\nrespective contributions to the reaction dynamics, new tools are needed.\nWe developed a new tool, ResiDEM, which employs a clustering-based\napproach to group difference electron densities and associate them\nwith proximal residues. It can identify and rank residues with significant\nmotions. Network representation can be used to delineate the interrelations\nbetween the residues in motion. With these features, ResiDEM helps\nto interpret residual motions in TR-SFX data, identify key residues,\nand elucidate their roles in dynamic processes.