Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/28596
English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 18076/20274 (89%)
造訪人次 : 5294726      線上人數 : 1349
RC Version 7.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜尋範圍 查詢小技巧：
  • 您可在西文檢索詞彙前後加上"雙引號"，以獲取較精準的檢索結果
  • 若欲以作者姓名搜尋，建議至進階搜尋限定作者欄位，可獲得較完整資料
    •  進階搜尋


    請使用永久網址來引用或連結此文件: https://ir.cnu.edu.tw/handle/310902800/28596


    標題: Ibalizumab-Human CD4 Receptor Interaction: Computational Alanine Scanning Molecular Dynamics Studies
    作者: Su, Zhi-Yuan
    貢獻者: 資訊管理系
    關鍵字: Antibody drugs
    drug resistance
    human immunodeficiency virus type 1 (HIV-1)
    Ibalizumab
    molecular dynamics
    Robetta alanine-scanning mutagenesis method
    日期: 2014
    上傳時間: 2015-05-06 21:21:57 (UTC+8)
    出版者: Bentham Science Publ Ltd
    摘要: Antibody drugs are used in the treatment of many chronic diseases. Recently, however, patients and doctors have encountered problems with drug resistance, and improving the affinity of antibody drugs has therefore become a pressing issue. Ibalizumab is a humanized monoclonal antibody that binds human CD4, the primary receptor for human immunodeficiency virus type 1 (HIV-1). In this study, we sought to identify the key residues of the complementarity-determining regions (CDRs) of ibalizumab. Virtual alanine mutations (complementarity-determining regions of ibalizumab) were also studied using solvated interaction energies derived from molecular dynamics and the explicit water model. Using 1,000 nanosecond molecular dynamic simulations, we identified six residues: Tyr50 [HCDR2], Tyr53 [HCDR3], Asp58 [HCDR2], Glu95 [HCDR2], and Arg95 [LCDR3]. The Robetta alanine-scanning mutagenesis method and crystallographic information were used to verify our simulations. Our simulated binding affinity of -17.33 kcal/mol is close to the experimentally determined value of -16.48 kcal/mol. Our findings may be useful for protein engineering the structure of the ibalizumab-human CD4 receptor complex. Moreover, the six residues that we identified may play a significant role in the development of bioactive antibody analogues.
    關聯: Current Computer-Aided Drug Design, v.10 n.3, pp.217-225
    顯示於類別:[資訊管理系] 期刊論文

    文件中的檔案:

    檔案 描述 大小格式瀏覽次數
    index.html0KbHTML1805檢視/開啟


    在CNU IR中所有的資料項目都受到原著作權保護.

    TAIR相關文章

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回饋