Molecular Docking, Drug-Likeness and ADMET Analysis, Application of Density Functional Theory (DFT) and Molecular Dynamics (MD) Simulation to the Phytochemicals from Withania Somnifera as a Potential Antagonist of Estrogen Receptor Alpha (ER-α)

Introduction: Breast cancer is one of the leading causes of death of women every year. Estrogen receptor alpha (ER-α) is an important pathway that is responsible for the development of breast cancer. Tamoxifen is the most commonly used to treat breast cancer. But the main drawback of using the drug is that it increases the risk of uterine cancer, stroke,and pulmonary embolism.

Methods: In this research, the in-silico approach was followed to get the anticancer agent from Withania somnifera as the root extract of the plant is active against breast cancer. For this, 15 bioactive molecules were subjected to molecular docking and got 9 molecules comparing the consensus binding affinity of H3B-9224.

Results: After rescoring, drug-likeness analysis, and ADMET analysis of the molecules were done and 3 molecules remained. These 3 molecules showed good ADMET properties which arecrucial requirements in the drug discovery process. Their activity was checked by applying density functional theory (DFT) and all of them showed good reactivity. Their binding interaction was also evaluated.

Conclusion: Finally, the stability of those molecules checked by applying molecular dynamics (MD) simulation. After this simulation, 2 molecules remained that had good stability with the protein during the simulation period.

Keywords: ADMET; Breast cancer; Density functional theory; Drug-likeness; Molecular docking; Molecular dynamics (MD) simulation; Withania somnifera.