XDock: A General Docking Method for Modeling Protein-Ligand and Nucleic Acid-Ligand Interactions

Area of Science:

• Computational chemistry
• Structural biology
• Drug discovery

Background:

• Molecular docking is crucial for drug discovery and understanding biological mechanisms.
• Existing docking tools often lack universality for diverse molecular systems.
• A need exists for a versatile and accurate docking framework.

Purpose of the Study:

• To introduce XDock, a novel docking framework for protein-ligand and nucleic acid-ligand interactions.
• To develop a computationally efficient tool that accounts for ligand flexibility.
• To provide a universal solution for molecular docking challenges.

Main Methods:

• XDock utilizes a distance geometric method for ligand sampling and docking multiple conformations.
• It incorporates knowledge-based scoring functions for interaction assessment.
• The framework allows flexible refinement of predicted binding poses.

Main Results:

• XDock demonstrated high accuracy across diverse benchmarks of protein-ligand and nucleic acid-ligand complexes.
• Performance was validated against six established docking programs.
• The tool achieves an average docking time of under one minute per ligand.

Conclusions:

• XDock offers a versatile, accurate, and efficient solution for molecular docking.
• It supports both protein-ligand and nucleic acid-ligand docking.
• XDock is a valuable asset for structure-based drug discovery and biological investigations.