The XChemExplorer graphical workflow tool for routine or large-scale protein-ligand structure determination.

Area of Science:

• Structural biology
• Computational chemistry
• Drug discovery

Background:

• Established crystallographic software focuses on single structure analysis.
• Structure-based ligand discovery (SBLD) requires rapid analysis of numerous similar protein-ligand complexes.
• Efficient data management and workflow tools are crucial for SBLD.

Purpose of the Study:

• To introduce XChemExplorer (XCE), a novel data-management and workflow tool for SBLD.
• To provide an intuitive graphical user interface for the entire SBLD process.
• To demonstrate the scalability and utility of XCE in large-scale fragment-screening campaigns.

Main Methods:

• XCE offers a graphical user interface guiding users from data processing to data dissemination.
• It supports batch processing of multiple datasets and records metadata in an SQLite database.
• XCE integrates with existing crystallographic software, requiring only CCP4 installation.

Main Results:

• XCE facilitates the simultaneous analysis of numerous protein-ligand complexes.
• The tool enables efficient tracking of progress and annotation of structures.
• XCE has been successfully applied to fragment-screening campaigns, analyzing over 1000 datasets.

Conclusions:

• XChemExplorer is a scalable and effective tool for large-scale structure-based ligand discovery.
• XCE simplifies and accelerates the analysis of complex crystallographic datasets.
• The tool supports efficient drug design projects by managing large numbers of protein-ligand complexes.