Identification of therapeutic peptide scaffold from tritrpticin family for urinary tract infections using <i>in silico</i> techniques

Antimicrobial peptides (AMPs) like tritrpticins, exhibit non-specific membrane lysis of gram-negative bacteria and can replace antibiotics, combating multi-drug resistance observed in UTI patients. Tritrpticins designated – NT, T1, T2, T3, T5, T7 and T8, were computationally investigated by interaction with <i>Escherichia coli</i> membrane model, mammalian cell toxicity and structural stability to identify a potential drug scaffold for UTI. Initially T3 was eliminated due to low interaction with <i>Escherichia coli</i> membrane model, based on its computed solvation energy. Further, negative support vector machine (SVM) scores revealed non-toxicity of T1, T2, T5, T7 and T8. Finally, at 310 K and varying pH 4.5–9.0, T5 exhibited highest structural stability based on its highest consistency of hydrogen bonds (H-bonds), root mean square deviation (RMSD) and secondary structure profiles along with its lowest conformational free energy. Overall, T5 could be considered a promising peptide drug scaffold to combat UTI. ABBREVIATIONSAMPantimicrobial peptidePBEQPoisson Boltzmann equationH-bondshydrogen bondsMICminimum inhibitory concentrationLD50lethal dose, 50%RMSDroot mean square deviationSVMsupport vector machineUTIurinary tract infection antimicrobial peptide Poisson Boltzmann equation hydrogen bonds minimum inhibitory concentration lethal dose, 50% root mean square deviation support vector machine urinary tract infection Communicated by Ramaswamy H. Sarma