Providing a method for analyzing interaction between biomolecules having multiple recognition mechanisms

• Project/Area Number: 15K00406
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Life / Health / Medical informatics
• Research Institution: Kitasato University
• Principal Investigator: Ueno-Noto Kaori 北里大学, 一般教育部, 講師 (20361818)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: 生体分子シミュレーション / 抗体 / 糖鎖 / 分子間相互作用 / ヒト免疫不全ウィルス

Outline of Final Research Achievements

This study aims to provide a method for elucidating ligand binding of a biomolecule having multiple recognition mechanisms. Neutralizing antibodies 2G12 and PGT have shown to bind directly to the Human immunodeficiency virus-1 envelope glycoprotein via glycans on the glycoprotein. A model focused on the water molecules inside biomolecules was applied to glycan-antibody complexes and properly depicted the interaction between glycans and the antibody. Details of the interaction between the PGT128 antibody and the glycoprotein were analyzed based on quantum chemical calculations and molecular dynamics simulations using the crystal structures of the PGT128-glycoprotein complex. Two glycans played significant roles in the antibody-glycoprotein binding. Glycan-glycan interactions were also contributed to the binding. The glycan binding specificities of PGT antibodies were also theoretically compared, and obtained interaction energies agreed well with the experimental results.

Research Products

• [Journal Article] Water Molecules Inside Protein Structure Affect Binding of Monosaccharides with HIV-1 Antibody 2G12 (2016)
  • Author(s): K. Ueno-Noto, K. Takano
  • Journal Title: J. Comp. Chem. Volume: 37 Issue: 26 Pages: 2431-2438
  • DOI: 10.1002/jcc.24447
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] An application of an explicit water model to a glycoprotein-antibody complex (2018)
  • Author(s): Kaori Ueno-Noto
  • Organizer: 日本化学会第98春季年会
• [Presentation] Theoretical study of the interaction between a neutralizing antibody and glycan ligands on the HIV-1 Envelope glycoprotein (2017)
  • Author(s): K. Ueno-Noto
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 慶応大学（神奈川県横浜市）
  • Year and Date: 2017-03-17
• [Presentation] Interaction Analysis between HIV-1 and PGT antibodies (2017)
  • Author(s): M. Kusumoto, K. Noto, K. Takano
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 慶応大学（神奈川県横浜市）
  • Year and Date: 2017-03-17
• [Presentation] A theoretical study of the recognition of a neutralizing antibody to the HIV-1 envelope glycoprotein (2017)
  • Author(s): Kaori Ueno-Noto
  • Organizer: World Association of Theoretical and Computational Chemists (WATOC) 2017
  • Int'l Joint Research
• [Presentation] HIV-1 外被糖タンパク質における糖鎖―中和抗体間相互作用に関する理論的研究 (2017)
  • Author(s): 能登 香
  • Organizer: 第36回日本糖質学会年会
• [Presentation] フラグメント分子軌道法によるHIV-1認識PGT抗体と抗原糖鎖との間の相互作用解析 (2017)
  • Author(s): 楠本美侑，能登香，鷹野景子
  • Organizer: 第11回分子科学討論会
• [Presentation] The effect of water molecules on the binding affinity of the ligands to the HIV-1 antibody 2G12 (2016)
  • Author(s): K. Ueno-Noto, K. Takano
  • Organizer: heory and Applications of Computational Chemistry (TACC-2016)
  • Place of Presentation: ワシントン大学（シアトル，米国）
  • Year and Date: 2016-08-29
  • Int'l Joint Research
• [Presentation] 大規模量子化学計算によるHIV-1表面糖タン パク質と中和抗体間の相互作用解析 (2016)
  • Author(s): 能登 香
  • Organizer: 日本化学会第96春季年会
  • Place of Presentation: 同志社大学（京都府京田辺市）
  • Year and Date: 2016-03-25
• [Presentation] Affinity of HIV-1 antibody 2G12 with monosaccharides: a theoretical study based on explicit and implicit water models (2015)
  • Author(s): ○Kaori Ueno-Noto, Yuka Koyama,Keiko Takano
  • Organizer: PACIFICHEM 2015
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2015-12-19
  • Int'l Joint Research
• [Presentation] 複数箇所で抗原を認識する抗体における分子間相互作用に関する理論研究 (2015)
  • Author(s): 能登 香
  • Organizer: 第9回分子科学討論会
  • Place of Presentation: 東京工業大学（東京都目黒区）
  • Year and Date: 2015-09-19
• [Presentation] HIV-1中和抗体PGTと糖タンパク質gp120複合体における分子間相互作用の電子論的考察 (2015)
  • Author(s): 能登 香
  • Organizer: 第34回日本糖質学会年会
  • Place of Presentation: 東京大学（東京都文京区）
  • Year and Date: 2015-08-01
• [Remarks]
  • URL: https://www.kitasato-u.ac.jp/ippan/kagaku/noto.html
• [Remarks] 北里大学研究者情報データベース
  • URL: http://kerid-web.kitasato-u.ac.jp/Profiles/45/0004485/profile.html
• [Remarks] 北里大学一般教育部自然科学教育センター化学
  • URL: https://www.kitasato-u.ac.jp/ippan/kagaku/noto.html