Online Mutator application

• The algorithm, named Mutator, makes limited amino acid substitutions on natural peptide antibiotics (preferably of anuran origin) in order to improve their therapeutic index (TI)*.
• It has five modules, three suggesting single amino acid substitution and two suggesting double substitutions. No substitution is suggested in any of the modules if they are unable to predict the increase higher than 10 with respect to a TI calculated/predicted for a query sequence.
• The Double Mutator module is most effective when the suggested substitutions are positioned near the peptide termini and increase the peptide’s net charge.
• To use Mutator:
  • Paste the sequence to be analysed, in single letter amino acid code, into the window below.
  • Check which module gives the highest TI.
  • (Optional) Repeat the procedure, by pasting the best mutated sequence in the query window, until a TI >85 is predicted. Because all Mutator modules use the D-descriptor model [1], which gives a maximum predicted TI = 95, this is effectively the limit of suggested improvement.
  • (Optional) You can further check the prediction by pasting suggested sequences in the Therapeutic Index Estimator server at http://split4.pmfst.hr/split/dserv1/. This predicts a TI value for a sequence based on the same D-descriptor model, so it should be in complete agreement with the TI values calculated by Mutator modules.

*The therapeutic index is defined as the TI =HC50/MIC, where HC50 is the peptide concentration causing hemolysis of 50% human erythrocytes, while MIC is minimal peptide concentration inhibiting bacterial growth after overnight incubation at 37°C. A high measured value is relevant for peptide antibacterial selectivity and low toxicity to human cells.