In silico Studies of Parasporin Proteins: Structural and Functional Insights and Proposed Cancer Cell Killing Mechanism for Parasporin 5 and 6

Background: Cancer is the leading cause of death in the world and the new types of cancer are diagnosed regularly but the advancement in their treatment is relatively slow and not to mention very costly. Parasporins (PS), parasporal inclusion proteins from Bacillus thuringiensis, possess specific cytotoxicity against different cancer cells which has suggested them to be potential for cancer treatment due to their specific binding to cancer cells. Methods: Computational investigation were performed to exploit their physicochemical characteristics, structural properties including three dimensional (3D) model, model quality analysis, phylogenetic assessment and functional analysis along with the cancer-cell killing mechanism of PS-5 and PS-6 proteins using standard tools of bioinformatics. Results: PS proteins were found to be slightly acidic based on their isoelectric points i.e., pI ranging from 5.12- 6.19, and the instability indices (29.03- 42.31) indicate their highly stable nature in test tubes and higher aliphatic indices (62.54-94.75) indicate their thermostability, a feature suitable for high-level industrial production. In silico analysis of cellular localization predicts that the parasporins are mostly located in the cytoplasm and few in the plasma membrane but devoid of any signal peptide. The generated 3D models of PS proteins upon verification by Ramachandran plot analysis confirmed that our prediction lies in the good quality model range and facilitated the understanding of the very protein folding, assembly into complexes and cell killing mechanisms. It could be hypothesized that the PS-5 protein might induce apoptosis or act as β- pore forming toxin to kill specific cancer cells while PS-6 might act simply as pore forming toxin. Conclusion: The theoretical overview of this research would facilitate the researchers with valuable insights of the PS protein structures, cancer cell killing mechanism of PS-5 and PS-6 proteins eventually in tumor micro-environment and their receptor molecules with a view to develop anti-cancer drugs.