Cat_Wiz: a stereochemistry-guided toolkit for locating, diagnosing, and annotating Mg2+ ions in RNA structures

Area of Science:

• Structural Biology
• Computational Biology
• Biochemistry

Background:

• Misassigned magnesium (Mg2+) ions are a significant issue in RNA structural databases.
• These errors hinder mechanistic interpretation, comparative analyses, and machine learning model training.

Purpose of the Study:

• To introduce Cat_Wiz, a Coot-integrated toolkit for localizing, diagnosing, correcting, and annotating Mg2+ binding sites in RNA.
• To establish robust standards for RNA-ion assignments using stereochemical principles.

Main Methods:

• Cat_Wiz utilizes stereochemistry-guided principles derived from ribosome and Cambridge Structural Database (CSD) analyses.
• It features three modules: MG_diagnosis for validation, MG_detect for identifying unmodeled sites, and MG_clamp for motif classification.
• A comprehensive binding site annotation system is included.

Main Results:

• Cat_Wiz rapidly locates overlooked Mg2+ ions and corrects misassignments in various RNA structures (ribosomes, ribozymes, introns).
• The toolkit significantly improves stereochemical fidelity, reducing correction time from days to hours.
• Generated data can be used to train machine learning and artificial intelligence (AI) models.

Conclusions:

• Cat_Wiz provides a transparent, cost-effective, and reproducible framework for RNA-ion assignment.
• Accurate Mg2+ site identification will advance RNA 3D architecture design by revealing Mg2+-dependent folds.
• The toolkit's principles are applicable to Mg2+ binding sites in proteins and other biomolecular systems.