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

Abstract

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 Escherichia coli 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 Escherichia coli 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 infectionCommunicated by Ramaswamy H. Sarma