基于2009甲型H1N1流感病毒神经氨酸酶的分子对接研究  

Molecular docking study based on 2009 H1N1 influenza neuraminidase

作　　者：靳玉瑞[1] 李爱秀[1,2] 邓联柏[1] 罗力[1] 李凯[1] 

机构地区：[1]中国人民武装警察部队后勤学院基础部药物设计实验室,天津300309 [2]中国人民武装警察部队后勤学院,职业与环境危害生物标志物天津市重点实验室,天津300309

出　　处：《计算机与应用化学》2014年第3期298-302,共5页Computers and Applied Chemistry

基　　金：国家自然科学基金项目(81241114,30472166);天津市科技攻关计划重点科技攻关专项基金资助项目(06YFGZSH07000)

摘　　要：神经氨酸酶(NA)是流感病毒复制过程中的关键酶,基于NA结构设计的抑制剂(NAI)已成为临床上最主要的抗流感病毒药物。由于2009甲型H1N1流感病毒NA(09N1)与以往NA亚型的三维结构不同,对09N1的深入研究可为新型NAI的设计打开思路。本文利用分子对接软件GOLD和Surflex-Dock对09N1-NAI复合物(09N1体系)进行对接研究,采用配体对接构象的RMSD值和KISS score值(复合物晶体结构中氢键作用的重现率)等两项指标评价分子对接效果,并进一步分析NAI与09N1之间的相互作用。结果:所有配体得分最高构象的RMSD值均小于2.0 A,且KISS score值均较高,在GOLD对接中,基于打分函数GoldScore的对接结果优于ChemScore.氢键作用、静电作用、疏水作用和范德华力在配体对接构象得分中均占一定比例。结论;GOLD和Surflex-Dock对09N1体系的分子对接均具有一定可靠性,在GOLD对接中宜选GoldScore作为打分函数;通过对接验证了氢键作用、静电作用和疏水作用在NAI与NA结合中的重要性,提出范德华力对分子间的相互作用也有重要贡献。Neuraminidase （NA） is a key enzyme during the replication process of influenza virus, and inhibitors designed based on NA structures have been the main anti-flu drugs clinically. As NA from 2009 H1N1 influenza virus （09N1） has a different three dimensional structure from any other NA subtype, further research of 09N1 may provide opportunities for the design of new NA inhibitors （NAIs）. In this article, molecular docking sofiwares GOLD and Surflex-Dock were used to dock NAIs back to 09N1 from crystal complexes, with RMSDs and KISS scores （H-bonds repetition rate in 09N1-NAI complexes） of ligand docking conformations as criteria to check the reliability of both sol,wares. Based on the docking results, interactions between NAI and 09N1 were analyzed. Results： All the ligand docking conformations had RMSDs less than 2.0A and high KISS scores, and performance based on scoring function GoldScore was better than ChemScore during GOLD docking. H-bond interaction, electrostatic interaction, hydrophobic interaction and Van der Waals force all account for certain proportions in the docking scores. Conclusion： Both GOLD and Surflex-Dock have shown themselves reliable docking softwares for 09N1 system, and it＇s better to choose GoldScore as scoring function of GOLD. H-bond interaction, electrostatic interaction and hydrophobic interaction were validated to play important roles during the combination of NAI and NA, and Van der Waals force was also suggested to contribute greatly in the process.

关 键 词：神经氨酸酶 2009甲型H1N1 抑制剂 分子对接 相互作用 

分 类 号：TQ015.9[化学工程] TP391.9[自动化与计算机技术—计算机应用技术]