Introduction: Molecular docking provides a comprehensive framework for understanding drug–protein interactions, from the initial identification of active compounds to the evaluation of their long-term stability. This approach is particularly valuable in addressing drug resistance in cancer and in developing personalized therapeutic strategies. In this study, the anticancer drug paclitaxel (PTX) was investigated for its molecular interactions with the key regulatory protein Bcl-2 using docking-based approaches.
Methods: Structural data of PTX and Bcl-2 were retrieved from the Protein Data Bank (PDB) and the National Center for Biotechnology Information (NCBI). Docking simulations were performed using AutoDock Vina and Molegro Virtual Docker, followed by visualization and interaction analysis with PyMOL. To assess the binding specificity of PTX, its docking energy was compared against a set of 240 randomly selected ligands.
Results: Docking analysis revealed that PTX forms strong interactions with key amino acid residues GLY145, ARG146, and TYR108 of the Bcl-2 protein. The binding energy of PTX demonstrated a significantly higher affinity compared with the random ligand dataset, confirming its preferential binding to Bcl-2.
Conclusion: Overall, this study highlights the molecular interactions of paclitaxel with the anti-apoptotic protein Bcl-2, providing mechanistic insights into its antitumor activity. These findings may serve as a foundation for the rational design of more effective anticancer agents targeting Bcl-2-mediated pathways.