Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
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Molecular Orbital Study of the Formation of Intramolecular Hydrogen Bonding of a Ligand Molecule in a Protein Aromatic Hydrophobic Pocket
Jun KosekiHiroaki GoudaShuichi Hirono
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2016 Volume 64 Issue 7 Pages 1031-1035


The natural product argadin is a cyclopentapeptide chitinase inhibitor that binds to chitinase B (ChiB) from the pathogenic bacteria Serratia marcescens. Nω-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.

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© 2016 The Pharmaceutical Society of Japan
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