GM-Dock(Zn): a geometry matching-based docking algorithm for zinc proteins

摘要

Motivation: Molecular docking is a widely used technique for large-scale virtual screening of the interactions between small-molecule ligands and their target proteins. However, docking methods often perform poorly for metalloproteins due to additional complexity from the three-way interactions among amino-acid residues, metal ions and ligands. This is a significant problem because zinc proteins alone comprise about 10% of all available protein structures in the protein databank. Here, we developed GM-Dock(Zn) that is dedicated for ligand docking to zinc proteins. Unlike the existing docking methods developed specifically for zinc proteins, GM-Dock(Zn) samples ligand conformations directly using a geometric grid around the ideal zinc-coordination positions of seven discovered coordination motifs, which were found from the survey of known zinc proteins complexed with a single ligand.