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第 36 卷第 1 期 精 细 化 工 Vol.36, No.1
201 9 年 1 月 FINE CHEMICALS Jan. 2019

生物工程
HEPT 类 HIV-1 逆转录酶衍生物的 CoMFA、

CoMSIA 及 HQSAR 分析

仝建波，雷 珊，王 洋，秦尚尚

（1. 陕西科技大学 化学与化工学院，陕西 西安 710021；2. 教育部轻化工助剂化学与技术重点实验室，
陕西 西安 710021）

摘要：采用比较分子力场分析法（CoMFA）、比较分子相似因子分析法（CoMSIA）和分子全息定量结构关系
（HQSAR）对 1-[(2-羟乙氧)甲基]-6-苯硫基胸腺嘧啶（HEPT）类衍生物进行了分子活性构象选择、分子叠合、
空间力场范围建立以及相应 3D-QSAR 模型建立。结果表明：该法所建模型对此类化合物具有良好的预测能力。
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CoMFA 模型显示，交叉验证系数（q ）为 0.565，非交互验证系数（r ）为 0.892；CoMSIA 模型显示，最佳 q 2
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为 0.636，r 为 0.953；最佳的 HQSAR 模型显示，q 为 0.876，r 为 0.929，最佳全息长度为 97。根据三维等势
图和 HQSAR 色码图设计了 7 个有较高活性的 HEPT 类化合物。
关键词：CoMFA；CoMSIA；HQSAR；HEPT 类衍生物；生物工程
中图分类号：O656 文献标识码：A 文章编号：1003-5214 (2019) 01-0057-10

CoMFA, CoMSIA and HQSAR Analysis of HEPT as
HIV-1 Reverse Transcriptase Inhibitors

TONG Jian-bo, LEI Shan, WANG Yang, QIN Shang-shang
（1. College of Chemistry and Chemical Engineering, Shaanxi University of Science & Technology, Xi'an 710021,
Shaanxi, China; 2. Shaanxi Key Laboratory of Chemical Additives for Industry, Shaanxi University of Science and
Technology, Xi'an 710021, Shaanxi, China）

Abstract: Comparative molecular field analysis (CoMFA), comparative molecular similarity indices
analysis (CoMSIA) and hologram quantitative structure-activity relationship (HQSAR) for 1-[(2-
hydroxyethyloxy)methyl]-6-phenylthio thymidine (HEPT) derivatives were used to have molecular active
conformation selection, molecular alignment, as well as the establishment of corresponding 3D-QSAR
model. The model established by this method had a good ability to predict these compounds. For CoMFA
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2
model, the cross-validated q value and non-cross-validated r value was 0.565 and 0.892, respectively. The
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best q value for CoMSIA model was 0.636 and r value was 0.953. The most effective HQSAR model was
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obtained with q value of 0.876 and r value of 0.929, and the best hologram length value was 97. Seven
highly active HEPT compounds were designed based on three-dimensional contour maps and HQSAR color
code map. Observations derived from these QSAR modeling study may provide a theoretical reference for
designing more active HEPT derivatives.
Key words: CoMFA; CoMSIA; HQSAR; HEPT derivatives; biological engineering
Foundation items: National Natural Science Foundation of China (21475081); Natural Science Foundation
of Shaanxi Province (2015JM2057); Graduate Innovation Fund of Shaanxi University of Science and
Technology

收稿日期：2018-06-04; 定用日期：2018-09-17; DOI: 10.13550/j.jxhg.20180405
基金项目：国家自然科学基金（21475081）；陕西省自然科学基础研究计划（2015JM2057）；陕西科技大学研究生创新基金
作者简介：仝建波（1975—），男，教授，博士，E-mail：jianbotong@aliyun.com。