RT Journal Article SR Electronic T1 MatchMaps: Non-isomorphous difference maps for X-ray crystallography JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.09.01.555333 DO 10.1101/2023.09.01.555333 A1 Brookner, Dennis E. A1 Hekstra, Doeke R. YR 2024 UL http://biorxiv.org/content/early/2024/01/02/2023.09.01.555333.abstract AB Conformational change mediates the biological functions of macromolecules. Crystal-lographic measurements can map these changes with extraordinary sensitivity as a function of mutations, ligands, and time. The isomorphous difference map remains the gold standard for detecting structural differences between datasets. Isomorphous difference maps combine the phases of a chosen reference state with the observed changes in structure factor amplitudes to yield a map of changes in electron density. Such maps are much more sensitive to conformational change than structure refinement is, and are unbiased in the sense that observed differences do not depend on refinement of the perturbed state. However, even minute changes in unit cell properties can render isomorphous difference maps useless. This is unnecessary. Here we describe a generalized procedure for calculating observed difference maps that retains the high sensitivity to conformational change and avoids structure refinement of the perturbed state. We have implemented this procedure in an open-source python package, MatchMaps, that can be run in any software environment supporting PHENIX and CCP4. Through examples, we show that MatchMaps “rescues” observed difference electron density maps for poorly-isomorphous crystals, corrects artifacts in nominally isomorphous difference maps, and extends to detecting differences across copies within the asymmetric unit, or across altogether different crystal forms.Synopsis MatchMaps is a generalization of the isomorphous difference map allowing for computation of difference maps between poorly-isomorphous and non-isomorphous pairs of crystallographic datasets. MatchMaps is implemented as a simple-to-use, python-based command-line interface.Competing Interest StatementThe authors have declared no competing interest.