In Silico Design of Antimicrobial Peptides from <i>Bungarus caeruleus</i> Proteome Targeting Ethionamide Resistance Regulator of <i>Mycobacterium tuberculosis</i>

Abstract In silico digestion of Bungarus caeruleus proteome using five enzymes yielded more than 1000 shorter peptide sequences. Further, the antibacterial peptide was predicted using the DBAASP server. Based on various physiochemical properties (including stability, half‐life, and ADMET), 11 peptides were taken for molecular docking. Ethionamide resistance regulator (EthR)‐peptide docking was performed using the HADDOCK server and the peptide sequence HGATVAVKQVNRCSKNHL shows the maximum binding affinity with EthR. The binding score was maximum for the peptide with −9.3 kcal/mol in comparison with the standard drug (Isoniazid) with −5.69 kcal/mol when analyzed with the PRODIGY server. The complex structure and interactions were stable during the 200 ns molecular dynamics simulations using Gromacs‐2023.1. The stability of the complex was analyzed in terms of root‐mean‐square deviation (RMSD), root‐mean‐square fluctuation (RMSF), radius of gyration, H‐bond, and SASA. MMPBSA analysis indicated that the free energy of interaction of EthR with the peptide and Isoniazid was between −36.15 kcal/mol and −6.95 kcal/mol, respectively.