A Congener-Substitution Strategy for Docking Heavy Metal Protein-Ligand Complexes with AutoDock Vina
- 1Department of Chemistry, University of Fribourg, Chemin Du Musée 9, Fribourg, Switzerland, 1700
- 2Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, Padua, Italy, 35131
Abstract
Molecular docking is widely used to predict ligand-protein interactions, but its application to transition metal complexes, particularly those containing second- and third-row elements, remains limited by the lack of explicit metal parameterization in commonly used programs such as AutoDock Vina. Here, we present a simple, practical strategy for docking heavy transition metal complexes without reparameterization: substituting the metal center with its first-row congener (e.g. Ru → Fe; Ir → Co) prior to docking. We applied this approach to a dataset of approximately 60 crystallographically characterized protein-ligand complexes containing Re, Ru, Os, Rh, Ir, Pt and Pd, and then focused on a streptavidin/avidin-biotin validation set of 18 crystallographically characterized protein-ligand complexes (4 Ru, 14 Ir) retrieved from the Protein Data Bank. The experimentally observed binding pose on the full set (rigid docking) was reproduced in 66% of cases, while for the streptavidin/avidin-biotin systems (flexible docking) the crystallography pose was fully or partially reproduced in 60% of cases (3/4 for the Ru systems and 8/14 for the Ir systems). Despite this outcome heterogeneity, the coordination geometry of the metal center and the broader protein-ligand interaction fingerprint were well preserved across the docked complexes, with a smaller perturbation observed for the Ru/Fe pair than for the Ir/Co pair, consistent with the higher pose-recovery rate obtained for the Ru systems. Overall, these results indicate that congener substitution offers a rapid, accessible route to docking second- and third-row transition metal complexes with unmodified AutoDock Vina, particularly in rigid docking, while revealing possible metal- and system-dependent limitations that should be considered when extending the strategy to other systems.
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BibTeX
@misc{nedyalkova2026congenersubstitution,
title = {{A Congener-Substitution Strategy for Docking Heavy Metal Protein-Ligand Complexes with AutoDock Vina}},
author = {Miroslava Nedyalkova and Simone Bernardotto and Fabio Zobi},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15009469/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009469/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A Congener-Substitution Strategy for Docking Heavy Metal Protein-Ligand Complexes with AutoDock Vina
AU - Miroslava Nedyalkova
AU - Simone Bernardotto
AU - Fabio Zobi
PY - 2026
DA - 2026/09/25
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009469/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009469/v1
AB - Molecular docking is widely used to predict ligand-protein interactions, but its application to transition metal complexes, particularly those containing second- and third-row elements, remains limited by the lack of explicit metal parameterization in commonly used programs such as AutoDock Vina. Here, we present a simple, practical strategy for docking heavy transition metal complexes without reparameterization: substituting the metal center with its first-row congener (e.g. Ru → Fe; Ir → Co) prior to docking. We applied this approach to a dataset of approximately 60 crystallographically characterized protein-ligand complexes containing Re, Ru, Os, Rh, Ir, Pt and Pd, and then focused on a streptavidin/avidin-biotin validation set of 18 crystallographically characterized protein-ligand complexes (4 Ru, 14 Ir) retrieved from the Protein Data Bank. The experimentally observed binding pose on the full set (rigid docking) was reproduced in 66% of cases, while for the streptavidin/avidin-biotin systems (flexible docking) the crystallography pose was fully or partially reproduced in 60% of cases (3/4 for the Ru systems and 8/14 for the Ir systems). Despite this outcome heterogeneity, the coordination geometry of the metal center and the broader protein-ligand interaction fingerprint were well preserved across the docked complexes, with a smaller perturbation observed for the Ru/Fe pair than for the Ir/Co pair, consistent with the higher pose-recovery rate obtained for the Ru systems. Overall, these results indicate that congener substitution offers a rapid, accessible route to docking second- and third-row transition metal complexes with unmodified AutoDock Vina, particularly in rigid docking, while revealing possible metal- and system-dependent limitations that should be considered when extending the strategy to other systems.
ER -