Sesamolin, a polyphenol with potential breast cancer therapeutic benefits: Unveiling insights through structural mining of surfacesome proteins

• This study discovers novel DPs targeting significant cell surface proteins involved in breast cancer. • Various publicly available databases are utilised to retrieve the DPs and CSPs. • E2F8-Sesamolin (proposed drug) is the best-fit when compared to Olaparib (conventional drug). Cell-surface proteins (CSPs) have been employed extensively in cancer research as diagnostic and prognostic markers as well as targets for the creation of anticancer drugs. Few attempts have been made so far to describe the surfaceome of breast cancer (BC) patients. For enabling effective BC therapy, the identification of novel druggable biomarkers is an earnest need. In this study, publicly available databases are utilised to identify CSPs associated with BC. We also predict significantly altered receptor-ligand interactions in BC to determine significant CSPs and druggable polyphenols (DPs) with therapeutic potential to combat the disease using systems biology methods. Here, polyphenols are assessed for their druggable properties and then initially docked with CSPs. Finally, five DPs are docked and simulated against the nine significant CSPs identified in BC. The preliminary result of the analysis reports E2F8-Sesamolin to be the best-docked protein-ligand complex with a binding energy of −51.160 ± 18.054 Kcal/mol which was then simulated and compared with Olaparib, an approved drug for BC treatment that came out to be −44.441 ± 18.127 Kcal/mol. MD simulation revealed that a Sesamolin formed more H-bonds, providing a more stable and compact protein-ligand complex with E2F8 as compared to Olaparib. The result was also supported by calculating solvent-accessible surface area and analyzing the radius of gyration and MM-PBSA binding energies. Expression, oncoprint, survival and functional enrichment profiles of the significant CSPs are also analyzed to gain deeper insight into the significant CSPs and their role in BC tumorigenesis. Thus, our findings suggest a potential role of Sesamolin that can further be studied in detail for BC therapeutics, which was found to target the E2F8, a CSP receptor in a stable manner. The results can be validated in an experimental setup to explore the potential therapeutic efficacy of Sesamolin in targeting various CSPs.