Molecular docking of the pentapeptide derived from rice bran protein as anticancer agent inhibiting both receptor and non-receptor tyrosine kinases.

The cationic pentapeptide Glu-Gln-Arg-Pro-Arg (EQRPR) belongs to the family of anti-cancer peptides with significant anti-cancer activity. However, the mechanism by which the peptide performs this activity is unknown. In this study, we explored the pharmaceutical profile of Glu-Gln-Arg-Pro-Arg pentapeptide and revealed its anticancer properties by in silico docking studies. Moreover, the effect of EQRPR behavior of the DPPC membrane was investigated by means of Langmuir monolayer technique and the results were discussed in terms of mutual interactions. To evaluate the binding mechanisms, the pentapeptide and its various D-amino acid substituted analogs were docked to both epidermal growth factor receptor (EGFR) tyrosine kinase and proto-oncogene tyrosine-protein kinase, Fyn. Simultaneous binding of the pentapeptides to both EGFR and Fyn proteins, which are receptor- and non-receptor-kinases, respectively, suggest that these peptides can be an effective agent for cancer treatment. Moreover, to show the potential of the investigated pentapeptides to overcome the generated mutation-related drug resistance to EGFR targeted therapies, molecular docking investigations of EQRPR and all its D-analogs were performed against the prospective targets: Wild type EGFRWT and mutant EGFRT790M. Erlotinib and TAK-285 were used as reference molecules. The strong interaction of the peptide with EGFRWT (from -9.24 to -9.75 kcal/mol) and the secondary mutant EGFRT790M (from -9.28 to -9.64 kcal/mol) observed in most cancer recurrence cases indicates its good potential to overcome drug resistance in cancer therapy. In addition, the pharmacological properties of the investigated pentapeptides were revealed by in silico ADME (Absorption, Distribution, Metabolism, Excretion) and toxicity analysis.Communicated by Ramaswamy H. Sarma.

Evaluation of anti-cancer and anti-covid-19 properties of cationic pentapeptide Glu-Gln-Arg-Pro-Arg, from rice bran protein and its d-isomer analogs through molecular docking simulations.

Bioactive peptides derived from food proteins are becoming increasingly popular due to the growing awareness of their health-promoting properties. The structure and mechanism of anti-cancer action of pentapeptide Glu-Gln-Arg-Pro-Arg (EQRPR) derived from a rice bran protein are not known. Theoretical and experimental methods were employed to fill this gap. The conformation analysis of the EQRPR pentapeptide was performed first and the obtained lowest energy conformer was optimized. The experimental structural data obtained by FTIR and CD spectroscopies agree well with the theoretical results. d-isomer introduced one-by-one to each position and all D-isomers of the peptide were also examined for its possible anti-proteolytic and activity enhancement properties. The molecular docking revealed avid binding of the pentapeptide to the integrins α5ß1 and αIIbß3, with Kd values of 90 nM and 180 nM, respectively. Moreover, the EQRPR and its D-isomers showed strong binding affinities to apo- and holo-forms of Mpro, spike glycoprotein, ACE2, and dACE2. The predicted results indicate that the pentapeptide may significantly inhibit SARS-CoV-2 infection. Thus, the peptide has the potential to be the leading molecule in the drug discovery process as having multifunctional with diverse biological activities.