Document Type : Original Article
Authors
Department of Biological Sciences, King Abdulaziz University, Jeddah 80200, Saudi Arabia.
Abstract
Breast cancer (BC) is still one of the major causes of death in females, mainly because of the uncontrollable proliferation of breast cells. In this study, we analyzed the potency of 2,4-Di-tert-butylphenol (2,4-DTBP), a natural compound, against cancer through computer programs like molecular docking and molecular dynamics (MD) simulations. Molecular docking was conducted with AutoDockTool to evaluate 2,4-DTBP's interaction with critical breast cancer proteins, specifically PIK3CA, ESR1, and PTEN. Binding affinities (kcal/mol) and inhibition constants were evaluated to determine notable protein-ligand interactions. Molecular dynamics (MD) simulations were performed using the CABS-flex webserver to assess the stability of these interactions via RMSF and binding free energy analyses. The study utilized multiple methodologies, including PASS prediction, ADME assessment, toxicity profiling, Lipinski’s Rule of Five, and evaluation of anticancer activity. Strong binding affinities of 2,4-DTBP towards important breast cancer proteins were found by the docking results; the binding energy values ranged from -5.25 to -7.86 kcal/mol. Meaningful binding energies of -7.86, -7.68, and -7.36 kcal/mol have been detected for PIK3CA, ESR1, and PTEN, respectively. Protein-ligand complex stability was validated by molecular dynamics simulations, and PTEN exhibited the most stable association because of its higher structural stiffness and lower RMSF values. The 2,4-DTBP demonstrated acceptable standards in every evaluated metric. According to the in-silico results, 2,4-DTBP exhibits encouraging potential as a strong inhibitor of significant breast cancer targets, specifically PTEN, PIK3CA, and ESR1, which calls for additional in-vitro and in-vivo studies to further investigate its efficacy in treating cancer.
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