Exploring Novel Anticancer Peptides: Evolutionary Prediction of Potential tRNA-Encoded Peptides for Targeted Therapies

tRNA-Encoded Peptides (tREPs) are novel functional peptides that show potential as anti-parasitic therapies. In this, in silico study were carried out to create tRNA-encoded peptides with the potential to target the Anti-Apoptotic B-Cell Lymphoma-2 (Bcl-2) protein associated with Cancer Cell Survival and Resistance. This study explores the potential of tREPs as a novel class of anticancer peptide candidates. The research begins by creating tREPs from genomic tRNA sequences and carefully selecting two promising candidates, Pep1 and Pep2, based on various properties, including toxicity and half-life. Molecular docking analyses of Pep1 and Pep2 with the BCL2 protein, a key player in cancer cell survival, demonstrate robust binding interactions with strong HADDOCK scores. Detailed binding interaction assessments unveil the presence of hydrophobic interactions and hydrogen bonds contributing to complex stability. Molecular dynamics simulations confirm the stability of both complexes overtime. The peptide Pep1 (DWIAWRHHNDIVSWLTCGP RFKSWS) exhibited a good binding affinity of -103.5 +/- 1.3 with RMSD values of 0.6 nm and binding free energy -26.41 kcal/mol, indicating its potential as an effective anticancer therapeutic agent. Thus, this study underscores the potential of tREPs as a new frontier in anticancer peptide research and sheds light on the molecular interactions that could target therapies for cancer treatment, with Pep1 emerging as a promising candidate. These findings contribute to the ongoing pursuit of innovative anticancer drug development strategies.