Investigating the inhibitory and penetrating properties of three novel anticancer and antimicrobial scorpion peptides via molecular docking and molecular dynamic simulation

The two types of bladder cancer, muscle invasive and non-muscle invasive (NMIBC), are among the most prevalent cancers worldwide. Despite this, even though muscle-invasive bladder cancer is more deadly, NMIBC requires more therapy due to a greater recurrence rate and more extended and expensive care. Immunotherapy, intravesical chemotherapy, cystoscopy, and transurethral resection (TUR) are among the treatments available. Crude scorpion venomand purified proteins and peptides, can suppress cancer metastasis in an in vitro or in vivo context, suppress cancer growth, halt the cell cycle, and cause cell apoptosis, according to an increasing number of experimental and preclinical studies. In this research, three novels discovered peptides (P2, P3 and P4. ProteomeXchange: PXD036231) from Buthotus saulcyi and, Odontobuthus doriae scorpions were used along with a peptide called pantinin (as a control). The phylogenetic tree showed that the peptides belong to Chaperonin HSP60, Chrysophsin2 and Pheromone-binding protein2, respectively. These peptides were docked with four known antigens, BAGE, BLCAP, PRAME and ROR1 related to bladder cancer and three bacterial antigens FliC, FliD and FimH to investigate their antimicrobial and anticancer properties. The results showed that peptides 2 and 3 have the best binding rate. The MD simulation results also confirmed the binding of peptides 2 and 3 to antigens. The penetration power of peptides 2 and 3 in the membrane of cancer cells and bacterial cells was also simulated, and the results of RMSD and PD confirmed it. QSAR suggests that peptides 2 and 3 can act as anti-cancer and anti-microbial peptides.Communicated by Ramaswamy H. Sarma

Automated summary

Bladder cancer, including muscle invasive and non-muscle invasive types, is a common worldwide cancer. Non-muscle invasive bladder cancer requires more therapy due to its higher recurrence rate and longer, more expensive care. Experimental studies have shown that crude scorpion venom and purified proteins and peptides can suppress cancer metastasis, inhibit cancer growth, stop cell cycle, and induce cell apoptosis. In this research, three novel peptides (P2, P3, P4) were discovered from scorpions and studied for their antimicrobial and anticancer properties. Peptides 2 and 3 showed the highest binding rate and were confirmed to penetrate the membrane of cancer cells and bacterial cells. QSAR analysis suggests that peptides 2 and 3 can act as anti-cancer and antimicrobial peptides.