On the hydration structure of the pro-drug GPG-NH2 and its derivatives

Molecular dynamics simulations were used to investigate the hydration and structure of the tripeptide GPG-NH2, and the effect of substituting a fluorine or hydroxyl group onto one of the Ca positions in the glycinamide portion of the molecule. The fluorinated and hydroxylated peptides both display a slight dehydration of the proline and glycinamide residues and a different conformation of the glycinamide residue backbone than the GPG peptide. These two effects result in a significant decrease in the water-mediated interactions between the Gly1 and glycinamide residues, which had previously been shown to nucleate beta turns in GPG-NH2.