An In silico Approach to Identify High Affinity Small Molecule Targeting m-TOR Inhibitors for the Clinical Treatment of Breast Cancer

Abstract

Breast cancer is the most frequent malignancy among women. It is a heterogeneous disease with different subtypes<br />defined by its hormone receptor. A hormone receptor is mainly concerned with the progression of the PI3K/AKT/<br />mTOR pathway which is often dysregulated in breast cancer. This is a major signaling pathway that controls the<br />activities such as cell growth, cell division, and cell proliferation. The present study aims to suppress mTOR protein<br />by its various inhibitors and to select one with the highest binding affinity to the receptor protein. Out of 40 inhibitors<br />of mTOR against breast cancer, SF1126 was identified to have the best docking score of -8.705, using Schrodinger<br />Suite which was further subjected for high throughput screening to obtain best similar compound using Lipinski's<br />filters. The compound obtained after virtual screening, ID: ZINC85569445 is seen to have the highest affinity with<br />the target protein mTOR. The same result based on the binding free energy analysis using MM-GBSA showed that<br />the compound ZINC85569445 to have the the highest binding free energy. The next study of interaction between the<br />ligand and receptor protein with the pharmacophore mapping showed the best conjugates, and the ZINC85569445 can<br />be further studied for future benefits of treatment of breast cancer.