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S-DABO类非核苷类逆转录酶抑制剂分子对接及Field-Based QSAR研究（英文）
  • ISSN号：1003-1057
  • 期刊名称：《中国药学：英文版》
  • 时间：0
  • 分类：R916[医药卫生—药学]
  • 作者机构：[1]北京大学医学部药学院化学生物学,北京100191, [2]北京大学医学部药学院天然药物及仿生药物国家重点实验室,北京100191
  • 相关基金：National Natural Science Foundation of China（Grant No.21172014,20972011,21042009,21272017 and 81172917）;Grants from the Ministry of Science and Technology of China（Grant No.2009ZX09301-010）
作者： 樊宁宁[1], 刘振明[2], 王孝伟[1], 刘俊义[1,2]
关键词： HIV-1逆转录酶, S-DABOs, 分子对接, 基于场的三维定量构效关系, HIV-1 reverse transcriptase, S-DABOs, Molecular docking, Field-based QSAR
中文摘要：

HIV-1逆转录酶抑制剂是鸡尾酒疗法,即高效抗逆转录病毒治疗的主要组成成分,S-DABO系列化合物及其类似骨架对HIV-1逆转录酶表现出良好的抑制活性。本文基于公共骨架叠合的方法生成了基于场的三维定量构效关系模型（Field-based QSAR model）,并通过高斯立体场、静电场、疏水场、氢键供体场、氢键受体场和芳环场来表征。对应的统计学参数训练集交叉验证相关系数RCV2为0.5949,相关系数R2为0.8421,测试集Q2为0.5486,测试集相关系数Pearson-r为0.7460。通过分子对接,分子结合口袋分析以及三维等势图分析,我们得到了关键的药效基团与相互作用：（i）化合物与氨基酸残基Tyr181,Tyr188,Trp229存在π-π相互作用,与His236之间存在σ-π相互作用;（ii）化合物与Lys101之间存在氢键,与Tyr188之间存在卤键。对接分析和Field-based QSAR模型可以为新型HIV-1逆转录酶抑制剂的设计提供借鉴和帮助。

英文摘要：

HIV-1 reverse transcriptase（RT） inhibitors are major components of HAART（highly active antiviral therapy）. The S-DABOs（dihydro-alkylthio-benzyl-oxopyrimidines） series and their similar skeletons have exhibited preferable activities to inhibit HIV-1 RT. In the present study, we generated field-based QSAR models using common structure alignment, which was characterized by Gaussian steric, electrostatic, hydrophobic, hydrogen bond donor, hydrogen bond acceptor and aromatic ring fields（R2 = 0.8421, RCV2 = 0.5949 for the training set, Q2 = 0.5486, Pearson-r = 0.7460 for the test set）. Docking, pocket surface and contour map analyses were carried out. Key pharmacophore features were investigated, including（i） π-π interaction with residue Tyr181, Tyr188 and Trp229, σ-π interaction with His236,（ii） hydrogen bond with residue Lys101 and halogen bond with residue Tyr188. The docking analysis and field-based QSAR models could provide reasonable guidance in the rational design of potent HIV-1 RT inhibitors.

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期刊信息
  • 《中国药学：英文版》
  • 中国科技核心期刊
  • 主管单位:中国科学技术协会
  • 主办单位:北京大学药学院
  • 主编：王夔
  • 地址：北京市学院路38号
  • 邮编：100083
  • 邮箱：zggy@mail.bjmu.edu.cn
  • 电话：010-82801713
  • 国际标准刊号：ISSN：1003-1057
  • 国内统一刊号：ISSN：11-2863/R
  • 邮发代号:
  • 获奖情况:
  • 国内外数据库收录:
  • 被引量:708