Directed evolution of hemagglutinin-binding peptides by in silico screening

Heptamer peptide sequences that bind to hemagglutinin of influenza virus were selected from a random peptide library and screened by docking simulation in silico. The affinity selection against hemagglutinins (H1 and H3 serotypes) was performed by using a phage-displayed peptide library. Two sequences were identified and had affinity for both HI and H3 serotypes. The virtual library containing 133 peptides was constructed in molecular modeling software based on one of the sequences. All of the virtual peptides were interacted with hemagglutinin (protein data bank code, 1HGG) by LigandFit (Accelrys, Inc.), and the binding affinity was evaluated by three scoring algorithms of Ligscore, PLP, and Ludi. Scores of several mutants increased, and the calculated poses suggested that these peptides interacted with the binding pocket of hemagglutinin as well as sialyllactose. We showed that the evolutionary computation was available in an improvement of peptide activity.