title: Molecular Orbital Study of the Formation of Intramolecular Hydrogen Bonding of a Ligand Molecule in a Protein Aromatic Hydrophobic Pocket.
abstract: The natural product argadin is a cyclopentapeptide chitinase inhibitor that binds to chitinase B (ChiB) from the pathogenic bacteria Serratia marcescens. N(ω)-Acetyl-L-arginine and L-aminoadipic acid of argadin form intramolecular ionic hydrogen bonds in the aromatic hydrophobic pocket of ChiB. We performed ab initio molecular orbital and density functional theory calculations to elucidate the role of this intramolecular hydrogen bonding on intermolecular interactions between argadin and ChiB. We found that argadin accrues large stabilization energies from the van der Waals dispersion interactions, such as CH-π, π-π, and π-lone pair interactions, in the aromatic hydrophobic pocket of ChiB, although intramolecular hydrogen bonding within argadin might result in loss of entropy. The intramolecular ionic hydrogen bonding formation canceled local molecular charges and provided good van der Waals interactions with surrounding aromatic residues.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Kitasato University.
authors.forename: Jun
authors.initials: J
authors.lastname: Koseki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Gouda
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hirono
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D002688:Chitinases / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; D010456:Peptides, Cyclic; C419444:argadin; D002688:Chitinases; C000601657:chitinase B, Serratia marcescens