همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Molecular Docking Analysis of Eugenol and Paclitaxel Targeting MRAS in Breast Cancer Therapy

نویسندگان :

Yaas Rowhani¹ Somayeh Reiisi²

1- دانشگاه شهرکرد 2- دانشگاه شهرکرد

کلمات کلیدی :

Molecular docking،MRAS protein،Eugenol،Paclitaxel،Binding energy

چکیده :

Breast cancer is the leading cause of cancer-related deaths among women globally, with its incidence rising worldwide (Smolarz, Nowak, 2022). MRAS, which has unique functions related to classical RAS oncoproteins, is significantly more expressed in estrogen receptor-negative than in estrogen receptor-positive breast carcinomas and is crucial for cell migration and differentiation, influencing cell polarity and prompting research into potential treatments (Chin, DeVries, 2006; Hess, Anderson, 2006; Young, Rodriguez, 2018). Eugenol has antioxidant and anti-inflammatory effects, and it can induce apoptosis in cancer cells while inhibiting their migration and viability through specific pathways (Ulanowska, Olas, 2022). Additionally, paclitaxel, a taxane chemotherapy agent, is a vital treatment for breast cancer, disrupting microtubule dynamics to stop cell division and induce apoptosis, significantly improving survival rates and reducing cancer recurrence risk (Jivani, Shinde, 2024). The aim of this study is to investigate the molecular interactions of eugenol and paclitaxel with the MRAS protein through protein docking, assessing their binding energies. This study will evaluate how these two compounds bind to and block the MRAS protein, which subsequently has inhibitory effects on downstream pathways. In this study, at first the three-dimensional structure of the MRAS protein and the ligand eugenol was obtained from the Protein Data Bank database and converted to Protein Data Bank format using Open Babel software. The two-dimensional structure of paclitaxel was also retrieved from the PubChem database and converted to three-dimensional format using Avogadro and Open Babel. Then, the protein docking with eugenol was initially conducted, followed using Chimera and AutoDock software to purify and remove excess molecules from the protein, repair amino acids, decreased protein energy level and adjust charges and hydrogen bonds. The PDBQT format was also generated. By using PyMOL, the active site of the protein was identified, which includes 14 amino acids such as Glycine 23, Aspartate 21, Lysine 127, and Asparagine 126 etc. A grid box specific to the active site was defined with dimensions of 36, 40, and 44 along the axes, corresponding to X = 4.874, Y = 10.022, and Z = 11.152. For the ligands, eugenol was docked first, followed by paclitaxel using AutoDock 4. The best binding energy for eugenol was -5.54 kcal/mol, exhibiting two hydrogen bonds. In contrast, the best binding energy for the paclitaxel conformer was -6.36 kcal/mol, with one hydrogen bond. The bond structures were visualized using PyRx, revealing that eugenol primarily interacted with amino acids Phenylalanine 38, Alanine 27, and Lysine 158 through hydrogen bonds with Serine 126 and Aspartate 129. Additionally, paclitaxel showed strong interactions with MRAS through amino acids Phenylalanine 38 and Lysine 127, predominantly forming hydrogen bonds with Glycine 23. In summary, both eugenol and paclitaxel can bind to MRAS with favorable ΔG values, which may induce cell cycle alterations and apoptosis while modulating key cellular proteins involved in migration and cell proliferation. This mechanism positions them as promising therapeutic agents for breast cancer.