咪唑甘油磷酸酯脱水酶与含氮杂环磷酸酯类抑制剂作用方式的分子模拟.pdf

物理化学学报( Wuli Huaxue Xuebao)
August
Acta Phys.-Chim.Sin.2011,27(8),1831-1838
183
[ Article」
www.whxb.pku.edu.cn
咪唑甘油磷酸酯脱水酶与含氮杂环磷酸酯类抑制剂作用
方式的分子模拟
申涛1杜凤沛1刘婷1姚广伟1吴峥1方萌萌
徐筱杰2路慧哲1
(中国农业大学理学院,北京100193;2北京大学化学与分子工程学院,北京100871)
摘要:国际上依据咪唑甘油磷酸赌脱水酶(IGPD)底物结构筛选,成功获得了一系列含氮杂环磷酸酯类化合物
作为IGPD抑制剂,然而IGPD与含氮杂环磷酸酯类抑制剂间的作用模式尚不清楚.本研究利用 gaussian0
程序,基于密度泛函理论B3LYP方法,选择6-31G*基组优化含氮杂环磷酸酯类化合物,在确定其稳定构象的
基础上利用分子对接、力学优化构建GPD与其含氮杂环磷酸酯类抑制剂相互作用的复合物结构,基于化合物
的电子结构(前线轨道能级及组成、原子电荷、自然键轨道等)复合物的空间结构(抑制剂识別IGPD的功能域、
分子间氢键、 van der Waals相互作用等)探讨了IGPD与含氮杂环磷酸酯类抑制剂作用方式,确定了含氮杂环
电荷分布、磷酸根离子电荷分布、前线轨道LUMO能级是影响抑制剂活性的内在因素,为进一步筛选、优化高效
的新型除草剂提供了重要信息
关键词:咪唑甘油磷酸酯脱水酶;抑制剂;分子对接;力学优化;密度泛函理论;前线轨道
中图分类号:O641
Molecular Simulation of the Interaction between Imidazole Glycerol
Phosphate Dehydrase and Nitrogen-containing Heterocyclic
Phosphate Inhibitors
SHEN Tao DU Feng-pei LIU Ting YAO Guang-wei WU Zheng
FANG Meng-meng XU Xiao-jie LU Hui-zhe
Institute of Science and Technology, China Agricultural University, Beijing 100193, P R. China
Institute of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P R. China)
Abstract: A series of nitrogen-containing heterocyclic compounds as imidazole glycerol phosphate
dehydrase ( IGPD)inhibitors were successfully screened based on IGPD substrates; however, the
mecanism is o r I is stud the B3YP density functional theory method with the 6-31g*basis
set as implemented in the Gaussian 03 program was selected to optimize the nitrogen-containing
hetero clic phosphates. These complex structures were constructed using molecular docking and
optimization. The mode of interaction was discussed with regards to their electronic structures(frontier
orbital energies and composition, the atomic charges, the natural bond orbital, etc ) and complex spatial
structures(recognition functional domains of the inhibior of GPD, intermolecular hydrogen bonding, v
der Waals interactions, etc. The charge dis ribution of the nitrogen-containing heterocycle, the phosphate
ion charge distribution, and the frontier orbital LUMO energy levels of the inhibitor were determined to be
intrinsic factors that affect inhibi or aci it The conclusion of our study will provide valuable information for
Received January 26, 2011; Revised: May 5, 2011 Published on Web: June 13, 2011
respondingauthorEmail:luhz2008@yahoo.com.cn;Tel:+86-10-62732507
The project was supported by the National Natural Science Foundation of China(20972184)and Chinese Universities Scientific Fund(2009]S38
国家自然科学基金(209721864和中央高校基本科研业务费专项资金(200938,20115030资助项目
C Editorial office of Acta Physico-chimica Sinica