Estrogen Receptor Alpha Binders for Hormone-Dependent Forms of Breast Cancer: e-QSAR and Molecular Docking Supported by X-ray Resolved Structures
Vijay H. Masand, Sami A. Al‐Hussain, Abdullah Yahya Abdullah Alzahrani, Aamal A. Al‐Mutairi, Rania A. Hussien, Abdul Samad, Magdi E. A. Zaki
Abstract
High Resolution Image Download MS PowerPoint Slide Cancer, a life-disturbing and lethal disease with a high global impact, causes significant economic, social, and health challenges. Breast cancer refers to the abnormal growth of cells originating from breast tissues. Hormone-dependent forms of breast cancer, such as those influenced by estrogen, prompt the exploration of estrogen receptors as targets for potential therapeutic interventions. In this study, we conducted e-QSAR molecular docking and molecular dynamics analyses on a diverse set of inhibitors targeting estrogen receptor alpha (ER-α). The e-QSAR model is based on a genetic algorithm combined with multilinear regression analysis. The newly developed model possesses a balance between predictive accuracy and mechanistic insights adhering to the OECD guidelines. The e-QSAR model pointed out that sp 2 -hybridized carbon and nitrogen atoms are important atoms governing binding profiles. In addition, a specific combination of H-bond donors and acceptors with carbon, nitrogen, and ring sulfur atoms also plays a crucial role. The results are supported by molecular docking, MD simulations, and X-ray-resolved structures. The novel results could be useful for future drug development for ER-α.