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.ABBREVIATIONSAMPantimicrobial peptidePBEQPoisson Boltzmann equationH-bondshydrogen bondsMICminimum inhibitory concentrationLD50lethal dose, 50%RMSDroot mean square deviationSVMsupport vector machineUTIurinary tract infectionCommunicated by Ramaswamy H. Sarma.

Identification of protegrin-1 as a stable and nontoxic scaffold among protegrin family - a computational approach.

Achieving both, nontoxicity and stability in antimicrobial peptides (AMP) is a challenge. This study predicts a structurally stable, nontoxic scaffold among the protegrin family, for future therapeutic peptide analogs. Protegrins (PG) are a class of pharmaceutically approved, in demand AMPs, which require further improvement in terms of nontoxicity and stability. Out of five protegrins viz., PG1, PG2, PG3, PG4 and PG5, PG1 has been predicted as best scaffold. Prediction was based upon sequential elimination of other protegrins, using computational methods to assess the extracellular bacterial membrane penetrability, nontoxicity and structural stability by geometric observables. Initially, PG2 and PG4 showing the lowest membrane penetrability and highest toxicity respectively, were screened out. Among the remaining three protegrins, PG1 displayed both lowest root mean square deviation and radius of gyration, with a considerable occupancy of seven H-bonds and established uniform secondary structure profile throughout its ensembles. Therefore, the authors claim the superiority of PG1 as a nontoxic stable scaffold among its family. Communicated by Ramaswamy H. Sarma.