Fig 1. Molecular structure compatibility of Novicidin (NVC) and Schiff base.

A) Helix NVC structure prediction using SWISS-MODEL based on the template PDB-ID: 4TQL (Biasini et al. 2014) showing the aromatic ring side chains of the C-terminal Tyr-Phe-COO^- on a helix ribbon. Positively charged amino acids on the ribbon are shown in blue, while neutral amino acids are shown in gray. After energy minimization (total -900 kJ·mol^-1), the distance between the aromatic rings was 5.4–8.9 Å. The distance between the aromatic rings and the charged center was 3.4–7.0 Å. B) Electrostatic potential of NVC calculated using DeepView v 4.1 (Guex and Peitsch 1997) and showing the C-terminus as the only “negative pocket” in the structure (arrow), represented by the carboxylic acid group surrounded by two aromatic rings. C) Relaxed Schiff base structure without a zinc ion, drawn using Chemwriter (Metamolecular, LLC, USA). The distance between aromatic rings was ~11.4–15.7 Å. D) Zinc-Schiff base structure drawn using Chemwriter showing a positive zinc atom surrounded by two aromatic rings on nearly perpendicular planes. The five nitrogen atoms resulted in a pentahedral shape (9 edges, 6 triangular faces), allowing maximum accessibility to the zinc ion from two opposing sides (edges ~3.3±0.06 Å compared with smaller edges with an average of ~2.5±0.13 Å). One of these sides opposes one aromatic ring, while the other allows for interactions with both rings. The flexibility and directionality in the zinc-Schiff base structure suggests that zinc can be actively accessed even after complexing with peptide. The distance between aromatic rings was ~2.4–6.0 Å. The distance between aromatic rings and charged center was ~1.8 Å. (atoms: red-oxygen, white-carbon, blue-nitrogen, light-blue-hydrogen).