青蒿素类药物与血红蛋白的分子对接及分子动力学模拟研究  

Molecular Docking and Molecular Dynamics Simulation of Artemisinin-like Drugs and Hemoglobin

作　　者：闫斌 韩丽红 YAN Bin;HAN Lihong(School of Basic Medicine,Putian University,Putian,Fujian Province,351100 China;Fujian Key Laboratory of Tumor Translational Medicine,Putian University,Putian,Fujian Province,351100 China)

机构地区：[1]莆田学院基础医学院,福建莆田351100 [2]莆田学院肿瘤转化医学福建省高校重点实验室,福建莆田351100

出　　处：《世界复合医学》2023年第4期35-39,共5页World Journal of Complex Medicine

基　　金：福建省卫生健康科研人才培养项目(2019-ZQNB-18);福建省自然科学基金项目(2020J01920);莆田市科技计划项目(2020SP004);莆田学院引进人才科研基金项目(2018091)。

摘　　要：目的研究血红蛋白与青蒿素系列药物的作用机制,开展青蒿素类药物与血红蛋白的分子对接及分子动力学模拟研究。方法以血红蛋白的晶体结构为基础,借助分子对接的手段分别构建了血红蛋白-青蒿素、血红蛋白-蒿甲醚、血红蛋白-二氢青蒿素的复合物结构模型,并开展了分子动力学模拟的研究。结果蒿甲醚、二氢青蒿素、青蒿素绝对结合能分别为16.98 kcal/mol、32.28 kcal/mol、40.75 kcal/mol。蒿甲醚结合能力最强(-34.41 kcal/mol),二氢青蒿素(-24.50 kcal/mol)其次,青蒿素(-14.51 kcal/mol)结合能力最差。对于蒿甲醚体系来说,范德华力(-42.01 kcal/mol)是结合中最重要的作用力,但是对于二氢青蒿素和青蒿素体系来说,它们的结合力是由范德华力、静电力和极性溶剂作用共同决定的,二氢青蒿素的静电力(-27.80 kcal/mol)要强于青蒿素的静电力(-11.23 kcal/mol)和蒿甲醚的静电力(-11.01 kcal/mol)。血红蛋白与蒿甲醚存在重要作用的残基数量要多于二氢青蒿素和青蒿素体系。结论3种药物与血红蛋白的结合能力强弱顺序是蒿甲醚>二氢青蒿素>青蒿素。由于蒿甲醚与血红蛋白有着很强的疏水相互作用,导致二者结合能力最强。Objective To study the mechanism of action between hemoglobin and artemisinin series drugs,and to carry out molecular docking and molecular dynamics simulation research of artemisinin drugs and hemoglobin.Methods Based on the crystal structure of hemoglobin,the complex structure models of hemoglobin-artemisinin,hemoglobin-artemisinin and hemoglobin-dihydroartemisinin were constructed by means of molecular docking,and the molecular dynamics simulation was carried out.Results The absolute binding energy of artemisinin,dihydroartemisinin and artemisinin were 16.98 kcal/mol,32.28 kcal/mol and 40.75 kcal/mol,respectively.The binding ability of artemisinin(-34.41 kcal/mol)was the highest,followed by dihydroartemisinin(-24.50 kcal/mol),and artemisinin(-14.51 kcal/mol)was the worst.The van der Waals force(-42.01 kcal/mol)is the most important binding force for arteether systems,but for dihydroartemisinin and artemisinin systems,their binding force is determined by van der Waals force,electrostatic force and polar solvent action.The electrostatic force of dihydroartemisinin(-27.80 kcal/mol)was stronger than that of artemisinin(-11.23 kcal/mol)and artem(-11.01 kcal/mol).The number of residues that have important effects on hemoglobin and artemisinin is more than that of dihydroartemisinin and artemisinin system.Conclusion The binding ability of the three drugs to hemoglobin was in the order of artemether>dihydroartemisinin>artemisinin.Due to the strong hydrophobic interaction between artem and hemoglobin,the binding ability of the two is the strongest.

关 键 词：青蒿素 二氢青蒿素 蒿甲醚 血红蛋白 分子对接 

分 类 号：R4[医药卫生—临床医学]