A Multi-Crystal Method for Extracting Obscured Signal from Crystallographic Electron Density

Macromolecular crystallography is relied on to reveal subtle atomic difference between samples (e.g. ligand binding); yet their detection and modelling is subjective and ambiguous density is experimentally common, since molecular states of interest are generally only fractionally present. The existing approach relies on careful modelling for maximally accurate maps to make contributions of the minor fractions visible (1); in practice, this is time-consuming and non-objective (2-4). Instead, our PanDDA method automatically reveals clear electron density for only the changed state, even from poor models and inaccurate maps, by subtracting a proportion of the confounding ground state, accuratel