Ranking multiple docking solutions based on the conservation of inter-residue contacts

Area of Science:

• Computational biology
• Structural bioinformatics
• Drug discovery

Background:

• Molecular docking is crucial for understanding protein complex interactions.
• Accurately ranking docking solutions (decoys) to identify native-like conformations remains a challenge.

Purpose of the Study:

• To introduce CONSRANK, a novel tool for ranking molecular docking solutions.
• To evaluate CONSRANK's effectiveness in identifying high-quality docking poses.

Main Methods:

• CONSRANK analyzes the conservation of inter-residue contacts within a set of docking decoys.
• It calculates a conservation rate for each contact and ranks decoys based on frequently observed contacts.
• The method was tested on 102 targets from RosettaDock, DOCKGROUND, and CAPRI benchmarks.

Main Results:

• CONSRANK consistently ranked native-like solutions highly across all tested benchmarks.
• The tool demonstrated significant enrichment of native-like solutions in top positions (e.g., 9.9x for CAPRI).
• CONSRANK outperformed CAPRI scorers on analyzed CAPRI targets and identified a high percentage of high/medium quality solutions.

Conclusions:

• CONSRANK is an effective and simple tool for ranking molecular docking solutions.
• Its contact conservation approach offers a robust method for identifying accurate protein-protein interaction models.
• CONSRANK is particularly useful for analyzing results from multiple docking programs, as seen in CAPRI.