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BRIEF RESEARCH REPORT article
Front. Bioinform.
Sec. Drug Discovery in Bioinformatics
Volume 5 - 2025 | doi: 10.3389/fbinf.2025.1536504
Quality over quantity: how to get the best results when using docking for repurposing
Provisionally accepted- 1Mexican Social Security Institute, Mexico City, Mexico
- 2Centro de Investigación Biomédica de Oriente (CIBIOR), Metepec, Mexico
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Molecular docking is among the fastest and most readily available computational tool to explore protein-ligand interactions. However, little effort is placed in assessing the quality of its results. In this paper, we compared eight free license docking programs to screen a drug library against the human target, phosphodiesterase 5A (PDE5A), to evaluate their ability to find its known ligand, sildenafil, and other ligands that became erectile dysfunction drugs because they inhibit this target. Gnina, was superior at identifying the known target because it offers a Convolutional Neural Network (CNN) score that ranks the quality of docking results. Using this CNN score improved ranking of known positives. ROC analysis revealed that all docking suites lack specificity, that is, they often misidentify true negatives. Employing a CNN score cutoff before ranking by docking affinity raised specificity with a small loss in sensitivity. After the cutoff, datasets became smaller but of higher quality. We propose a heuristic to produce relevant docking results, which includes the overall evaluation of the target on docking performance through ROC, and the improvement of candidate binder selection using a CNN score cutoff of 0.9.
Keywords: Docking, gnina, drug repurposing, Virtual screeening, Convolucional Neural Network (CNN), UCSF ZINC, Dock6, Autodock vina
Received: 29 Nov 2024; Accepted: 08 Apr 2025.
Copyright: © 2025 Dominguez-Ramirez, Anaya-Ruiz and Cortes-Hernandez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Lenin Dominguez-Ramirez, Mexican Social Security Institute, Mexico City, Mexico
Paulina Cortes-Hernandez, Centro de Investigación Biomédica de Oriente (CIBIOR), Metepec, Mexico
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.