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International Journal of Zoology and Applied Biosciences Research Article
Mechanistic insights into SMAD3 inhibition using molecular docking techniques
Vinothini, Lourdu Brissilla Mary Varghese, Devasena B, Kaaviya A A and Jenifer E
Year : 2025 | Pages: 447-450
Received on: 25/09/2025
Revised on: 21/10/2025
Accepted on: 24/11/2025
Published on: 01/12/2025
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Vinothini, Lourdu Brissilla Mary Varghese, Devasena B, Kaaviya A A and Jenifer E ( 2025).
Mechanistic insights into SMAD3 inhibition using molecular docking techniques
. International Journal of Zoology and Applied Biosciences, 10( 6), 447-450.
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Abstract
Smad3 is a crucial intracellular transcription factor activated downstream of the transforming growth factor-β (TGF-β) signaling pathway, playing a central role in fibrosis, cancer progression, and inflammatory diseases. Targeting Smad3 with selective small-molecule inhibitors has emerged as a promising therapeutic strategy. This study aims to explore Smad3–ligand interactions using computational molecular docking techniques to identify key binding residues, assess inhibitor stability, and provide mechanistic insights into inhibitory potential. A curated library of 25 reported and novel phytochemical compounds was prepared and optimized using ligand minimization protocols. The Smad3 crystal structure (PDB ID: specify if needed) was refined through energy minimization, followed by grid box generation around the MH2 functional domain. Docking was performed using AutoDock Vina, and ligand interactions were analyzed through hydrogen bonding, hydrophobic mapping, and binding energy scoring. Among the screened ligands, Compound S15 exhibited the highest binding affinity (−9.4 kcal/mol), forming stable hydrogen bonds with Ser360, Tyr226, and Pro270. Other compounds showed moderate binding profiles ranging from −6.1 to −8.2 kcal/mol. The interaction analysis indicates that competitive inhibition of the MH2 domain may prevent downstream Smad3 phosphorylation, dimerization, and nuclear translocation. Overall, this study provides computational evidence supporting the development of potent Smad3 inhibitors and offers structural rationale for future in vitro and in vivo studies.
Keywords
Smad3, TGF-β signaling, Molecular docking, In silico drug discovery, Protein ligand interaction.
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© The Author(s) 2025. This article is published by International Journal of Zoology and Applied Biosciences under the terms of the Creative Commons Attribution 4.0 International License (creativecommons.org), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
