INTERNATIONAL CONGRESS OF
PharmacoGenetics
Molecular Docking Analysis of Psammaplin A as a Potential MCL-1 Inhibitor in Colorectal Cancer
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Artemis Azad Aza,1,* Elena Ebrahimian,2 Reza Assaran-Darban ,3
1. Department of Biology, Faculty of Basic Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
2. Department of Biology, Faculty of Basic Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
3. Department of Biology Mashhad Branch, Islamic Azad University Mashhad Iran
- Introduction: Psammaplin A, a bromotyrosine-derived natural product isolated from marine sponges, has attracted considerable interest because of its diverse biological activities, including reported anticancer effects. Myeloid cell leukemia-1 (MCL-1), an anti-apoptotic member of the Bcl-2 family, is frequently upregulated in colorectal cancer and contributes to tumor cell survival, resistance to apoptosis, and therapeutic failure. Consequently, MCL-1 is regarded as a validated target for drug development in colorectal cancer. In the present study, we used molecular docking to computationally assess the binding potential of Psammaplin A to MCL-1, with the aim of prioritizing this compound for subsequent in vitro biochemical assays and cellular validation as a putative MCL-1 inhibitor.
- Methods: To conduct this study, The psammaplin A was retrieved from PubChem (CID: 6400741) as a ligand. the structure of the MCL-1 protein was downloaded from the RCSB Protein Data Bank (PDB) with the ID 5FDR and prepared using PyMOL. Both were prepared in AutoDockTools. The ligand and receptor were converted from PDB to PDBQT format and saved. Docking was performed using AutoDockVina. Ultimately, the best conformation was selected based on the lowest binding energy, and its complex with the receptor was analyzed through the PLIP to determine the binding site based on the type and residue numbers of the interactions and the binding strength based on the type and number of interactions. These results were also visualized in PyMOL.
- Results: According to the docking results, the lowest binding energy is -8.3 kcal/mol, which is a favorable feature for binding. PLIP analysis showed seven hydrophobic interactions. And nine hydrogen bonds and one salt bridge between psammaplin A and the residues of the receptor These interactions suggest a potentially stable binding mode, but Vina scores are approximate and further validation (re-docking of the co-crystallized ligand, MM-GBSA rescoring and MD simulations) followed by biochemical assays are required to confirm inhibitory activity.
- Conclusion: Psammaplin A may be a promising MCL-1 inhibitor for the treatment of colorectal cancer, as shown by the low binding energy, favorable docking metrics, and several strong stabilizing contacts between them. However, these computational findings are preliminary and require comprehensive in vitro biochemical testing and in vivo research to ascertain their inhibitory effectiveness and therapeutic potential.
- Keywords: MCL-1, Psammaplin A, Molecular Docking, Colorectal Neoplasms.
