Designing IL-24-P18 Fusion Protein Through Computational Engineering for Targeted Breast Cancer Therapy

Breast cancer is the second leading cause of cancer-related deaths throughout the world, and it remains one of the significant health challenges due to treatment limitations such as drug resistance and adverse side effects. Instead of developing novel treatment approaches, including radiotherapy and chemotherapy, their efficacy is trapped by non-specific toxicity and resistance. This study includes designing a novel chimeric protein combining Interleukin-24 (IL-24) and p18 peptides that are well-being to exhibit significant anticancer properties. The fusion protein, IL-24-P18, was developed to enhance specificity and minimize off-target effects in breast cancer treatment. We used silico techniques to predict this novel fusion protein construct’s structural, functional and therapeutic properties. The P18 peptide was fused to the N-terminal of IL-24 using an AEAAAKEAAAKA linker. The fusion protein was found to be nontoxic, non-allergenic and non-antigenic. The fusion protein was hydrophilic with a neutral charge, exhibiting soluble expression in E. coli and stable at varying conditions. Secondary and tertiary structure predictions showed well-defined alpha-helices and a stable 3D conformation. Molecular docking and interaction analysis further confirmed strong binding affinities with a score of –847.5 Kcal/mol between IL-24-P18 and breast cancer receptor proteins, indicating the potential for selective targeting. Moreover, the MD simulation results revealed the interaction stability of the designed fusion protein and receptor. The overall results of this Insilco study showed that IL-24-P18 fusion is a prospective novel candidate against breast cancer that has the potential to inhibit breast cancer with higher accuracy and fewer side effects as compared to already available treatments. Further, in vitro and clinical studies are required to validate its clinical applicability.