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

ABBREVIATIONSAMP

antimicrobial peptide

PBEQ

Poisson Boltzmann equation

H-bonds

hydrogen bonds

MIC

minimum inhibitory concentration

LD50

lethal dose, 50%

RMSD

root mean square deviation

SVM

support vector machine

UTI

urinary 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