TheXChemExplorergraphical workflow tool for routine or large-scale protein–ligand structure determination

Abstract

XChemExplorer(XCE) is a data-management and workflow tool to support large-scale simultaneous analysis of protein–ligand complexes during structure-based ligand discovery (SBLD). The user interfaces of established crystallographic software packages such asCCP4 [Winnet al.(2011),Acta Cryst.D67, 235–242] orPHENIX[Adamset al.(2010),Acta Cryst.D66, 213–221] have entrenched the paradigm that a `project' is concerned with solving one structure. This does not hold for SBLD, where many almost identical structures need to be solved and analysed quickly in one batch of work. Functionality to track progress and annotate structures is essential.XCEprovides an intuitive graphical user interface which guides the user from data processing, initial map calculation, ligand identification and refinement up until data dissemination. It provides multiple entry points depending on the need of each project, enables batch processing of multiple data sets and records metadata, progress and annotations in an SQLite database.XCEis freely available and works on any Linux and Mac OS X system, and the only dependency is to have the latest version ofCCP4 installed. The design and usage of this tool are described here, and its usefulness is demonstrated in the context of fragment-screening campaigns at the Diamond Light Source. It is routinely used to analyse projects comprising 1000 data sets or more, and therefore scales well to even very large ligand-design projects.