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Updated: Jul 9, 2025

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
MetalDock: An Open Access Docking Tool for Easy and Reproducible Docking of Metal Complexes
Matthijs L A Hakkennes1, Francesco Buda1, Sylvestre Bonnet1
1Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Abstract:
Despite the proven potential of metal complexes as therapeutics, the lack of computational tools available for the high-throughput screening of their interactions with proteins is a limiting factor toward clinical developments. To address this challenge, we introduce MetalDock, an easy-to-use, open access docking software for docking metal complexes to proteins. Our tool integrates the AutoDock docking engine with three well-known quantum software packages to automate the docking of metal-organic complexes to proteins. We used a Monte Carlo sampling scheme to obtain the missing Lennard-Jones parameters for 12 metal atom types and demonstrated that these parameters generalize exceptionally well. Our results show that the poses obtained by MetalDock are highly accurate, as they predict the binding geometries experimentally determined by crystal structures with high spatial reproducibility. Three different case studies are presented that demonstrate the versatility of MetalDock for the docking of diverse metal-organic compounds to different biomacromolecules, including nucleic acids.
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