Molecular Orbital Study of the Formation of Intramolecular Hydrogen Bonding of a Ligand Molecule in a Protein Aromatic Hydrophobic Pocket

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Author(s)

    • Koseki Jun Koseki Jun
    • Department of Pharmaceutical Sciences, School of Pharmacy, Kitasato University|Quantum Chemistry Division, Graduate School of Science, Yokohama City University
    • Gouda Hiroaki Gouda Hiroaki
    • Department of Pharmaceutical Sciences, School of Pharmacy, Kitasato University|School of Pharmacy, Showa University

Abstract

The natural product argadin is a cyclopentapeptide chitinase inhibitor that binds to chitinase B (ChiB) from the pathogenic bacteria <i>Serratia marcescens</i>. <i>N</i><sup>ω</sup>-Acetyl-L-arginine and L-aminoadipic acid of argadin form intramolecular ionic hydrogen bonds in the aromatic hydrophobic pocket of ChiB. We performed <i>ab initio</i> 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.

Journal

  • Chemical and Pharmaceutical Bulletin

    Chemical and Pharmaceutical Bulletin 64(7), 1031-1035, 2016

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130005160079
  • NII NACSIS-CAT ID (NCID)
    AA00602100
  • Text Lang
    ENG
  • ISSN
    0009-2363
  • NDL Article ID
    027451920
  • NDL Call No.
    Z53-D167
  • Data Source
    NDL  J-STAGE 
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