Structure-Based Multi-Targeted Molecular Docking and Dynamic Simulation of Soybean-Derived Isoflavone Genistin as a Potential Breast Cancer Signaling Proteins Inhibitor
Author:
Elkhalifa Abd Elmoneim O.1ORCID, Al-Shammari Eyad1, Kuddus Mohammed2ORCID, Adnan Mohd3ORCID, Sachidanandan Manojkumar4, Awadelkareem Amir Mahgoub1ORCID, Qattan Malak Yahia5, Khan Mohammad Idreesh6ORCID, Abduljabbar Sanaa Ismael7, Sarwar Baig Mirza8ORCID, Ashraf Syed Amir1ORCID
Affiliation:
1. Department of Clinical Nutrition, College of Applied Medical Sciences, University of Ha’il, Ha’il P.O. Box 2440, Saudi Arabia 2. Department of Biochemistry, College of Medicine, University of Ha’il, Ha’il P.O. Box 2440, Saudi Arabia 3. Department of Biology, College of Science, University of Ha’il, Ha’il P.O. Box 2440, Saudi Arabia 4. Department of Oral Maxillofacial Surgery and Diagnostics, College of Dentistry, University of Ha’il, Ha’il P.O. Box 2440, Saudi Arabia 5. Health Sciences Departments, College of Applied Studies and Community Service, King Saud University, Riyadh 11451, Saudi Arabia 6. Department of Clinical Nutrition, College of Applied Health Sciences in Ar Rass, Qassim University, Ar Rass 51921, Saudi Arabia 7. Microbial and Pharmaceutical Biotechnology Laboratory, Department of Pharmacognosy & Phytochemistry, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi 110062, India 8. Center for Virology, School of Interdisciplinary Science and Technology, Jamia Hamdard, New Delhi 110062, India
Abstract
Globally, breast cancer (BC), the second-biggest cause of cancer death, occurs due to unregulated cell proliferation leading to metastasis to other parts of the human organ. Recently, the exploration of naturally derived anticancer agents has become popular due to their fewer adverse effects. Among the natural products, soybean is a very well-known legume that contains important bioactive compounds such as diadazine, glycetin, genistein, and genistin. Therefore, keeping its therapeutic potential in mind, multi-targeted molecular docking and simulation studies were conducted to explore the potential role of soybean-derived isoflavone genistin against several breast cancer-signaling proteins (ER-alpha, ER-Beta, collapsin response mediator protein 2, CA 15-3, human epidermal growth factor receptor 2). A comparative study of the genistin-protein docked complex was explored to investigate its potential role in BC. The molecular binding energy (∆G) of the docked complex was calculated along with ADMET properties. The molecular docking score of genistin with ubiquitin-like protein activation complex-a type of Cancer Antigen (CA) 15.3 (PDB ID-2NVU, 5T6P, and 1YX8) showed the highest binding energy, ranging from −9.5 to −7.0 Kcal/mol, respectively. Furthermore, the highest docking scores of the complex were additionally put through molecular dynamics (MD) simulation analysis. MD simulations of the selected complex were performed at 100 ns to study the stability of the genistin-ubiquitin-like protein CA 15.3 complex, which appeared to be quite stable. Additionally, the ADMET study demonstrated that genistin complies with all drug-likeness standards, including Lipinski, Egan, Veber, Ghose, and Muegge. Therefore, based on the results, genistin can be considered as one of the potential drugs for the management and treatment of BC. In addition, the obtained results suggest that genistin could pave the way for new drug discovery to manage breast cancer and has potential in the development of nutraceuticals.
Funder
Scientific Research Deanship at University of Ha’il-Saudi Arabia
Subject
Paleontology,Space and Planetary Science,General Biochemistry, Genetics and Molecular Biology,Ecology, Evolution, Behavior and Systematics
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