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Systematic Interaction Analysis of Anti-Human Immunodeficiency Virus Type-1 Neutralizing Antibodies with High Mannose Glycans Using Fragment Molecular Orbital and Molecular Dynamics Methods.

Authors
  • Kusumoto, Miyu1
  • Ueno-Noto, Kaori2
  • Takano, Keiko1
  • 1 Department of Chemistry and Biochemistry, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo, 112-8610, Japan. , (Japan)
  • 2 Center for Natural Sciences, College of Liberal Arts and Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0373, Japan. , (Japan)
Type
Published Article
Journal
Journal of Computational Chemistry
Publisher
Wiley (John Wiley & Sons)
Publication Date
Jan 05, 2020
Volume
41
Issue
1
Pages
31–42
Identifiers
DOI: 10.1002/jcc.26073
PMID: 31565801
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

A series of broadly neutralizing antibodies called PGT have been shown to be bound directly to human immunodeficiency virus type-1 via high mannose glycans on glycoprotein gp120. Despite the sequence similarities of amino acids of the antibodies, their affinities to the glycan differ. Glycan-antibody interactions among these antibodies are systematically compared with quantum chemical fragment molecular orbital calculations and molecular dynamics simulations. The differences among structural stability of the glycan in the active site of the complexes and total interaction energies as well as binding free energies between the glycan and antibodies agree well with the experimentally shown affinities of the glycan to the antibodies. The terminal saccharide, Man D3, is structurally stable and responsible for the glycan-antibody binding through electrostatic and dispersion interactions. The structural stability of nonterminal saccharides such as Man 4 or Man C plays substantial roles in the interaction via direct hydrogen bonds. © 2019 Wiley Periodicals, Inc. © 2019 Wiley Periodicals, Inc.

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