受体蛋白与药物分子对接的研究进展

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (11): 1308-1312.

受体蛋白与药物分子对接的研究进展

朱志远¹, 张燕¹, 李征¹, 李金恒², 芮建中², 袁靖¹

¹中国人民解放军第86 医院药械科, 马鞍山243100, 安徽;
²南京军区南京总医院药理科, 南京210002, 江苏

收稿日期:2009-08-27 修回日期:2009-09-30 发布日期:2020-10-26
作者简介:朱志远, 男, 药师, 研究方向:临床药理学与分子生物学。Tel:13685557853 E-mail:zzyabraham2008@yahoo.com.cn

Progress in receptor protein &drug molecule docking approaches

ZHU Zhi-yuan¹, ZHANG Yan¹, LI Zheng¹, LI Jing-heng², RUI Jian-zhong², YUAN Jing¹

¹Department of Pharmacy, the 86th Hospital of PLA, Maanshan 243100, Anhui, China;
²Department of Clinical Pharmacology, Nanjing General Hospital of Nanjing Command, Nanjing 210002, Jiangsu,China

Received:2009-08-27 Revised:2009-09-30 Published:2020-10-26

摘要/Abstract

摘要： 计算机技术的发展极大地促进了生命科学研究进程。利用分子对接技术研究受体蛋白和药物相互作用是当前的热点课题。通过分别建立蛋白质和药物分子模型, 并对它们的相互作用进行研究, 进而为发现并设计出更加理想、安全、有效的药物打下深厚的基础。分子模型建立的问题已经得到很好的解决, 但是分子与分子间以什么方式对接、怎样对接等问题尚待深入研究。本文就当前分子对接的研究进展作一综述, 着重介绍了分子对接的方法和常用工具的研究情况。

关键词: 分子对接, 蛋白质柔性, 模型优化, 分子模拟

Abstract: The development of computer technology greatly facilitated the process of life science research.The study on the use of molecular docking receptor protein and drug interactions is the current hot spot.The molecular models of proteins and drugs are established and the interaction are studyed.In this way, the more ideal, safe and effective drugs are designed.The problem how to create the molecule model has been solved.Protein molecules and drug molecules docking in what manner, and this problem is worth exploring.This article describes the current research progress in molecular docking, emphasizing on its methods and tools.

Key words: molecular docking, protein flexibility, optimization model, molecular simulation

中图分类号:

R965.2

朱志远, 张燕, 李征, 李金恒, 芮建中, 袁靖. 受体蛋白与药物分子对接的研究进展[J]. 中国临床药理学与治疗学, 2009, 14(11): 1308-1312.

ZHU Zhi-yuan, ZHANG Yan, LI Zheng, LI Jing-heng, RUI Jian-zhong, YUAN Jing. Progress in receptor protein &drug molecule docking approaches[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(11): 1308-1312.

参考文献

[1] Comeau SR, Gatchell DW, Vajda S, et al.ClusPro:an automated docking and discrimination method for the prediction of protein complexes[J].Bioinformatics, 2004, 20(1):45-50.
[2] Rodrigues LF, Dupret JM.3D Model of Human Arylamine N-Acetyltransferase 2:Structural Basis of the Slow Acetylator Phenotype of the R64Q Variant and Analysis of the Active-Site Loop[J].Biochemi Biophysi Res Commun, 2002, 291(1):116-123.
[3] Lee K, Czaplewski C, Kim SY, et al.An efficient molecular docking using conformational space annealing[J].J Comput Chem, 2005, 26(5):78-87.
[4] Romkes M, Buch SC.Genotyping technologies:application to biotransformation enzyme genetic polymorphism screening[J].Methods Mol Biol, 2005, 291(4):399-414.
[5] Johnson JA, Turner ST.Hypertension pharmacogenomics: current satus and future directions[J].Curr Opin Mol Ther, 2005(1):218-225.
[6] Smellie A, Stanton R, Henne R, et al.Conformational analysis by intersection[J].Comput Chem, 2003, 24(3):10-20.
[7] Erickson JA, Jalaie M, Robertson DH, et al.Lessons in molecular recognition:the effects of ligand and protein flexibility on molecular docking accuracy[J].Med Chem, 2004, 47(2):45-55.
[8] Wu G, Robertson DH, Brooks CL, et al.Detailed analysis of grid-based molecular docking:A case study of CDOCKER- A CHARMm-basedMD docking algorithm[J].Comput Chem, 2003, 24(1):1549-1562.
[9] Irina K, Ruben A.Type-II Kinase Inhibitor Docking, Screening, and Profiling Using Modified Structures of Active Kinase States[J].J Med Chem, 2008, 51(8):24-26.
[10] 黄文奇, 黄勤波, 石赫.求解蛋白质结构预测问题的二维连续模型及其相应的拟物算法[J].计算机研究与发展, 2004, 41(11):1959-1965.
[11] Park K, Vendruscolo M, Domany E.Towards an energy function for the contact map representation of proteins[J]. Proteins:Structure, Function and Genntics, 2000, 40(2): 237-248.
[12] Goodfellow GH, Dupret JM, Grant DM.I dentification of amino acids imparting acceptor substrate selectivity to human arylamine acetyltransferases NAT1 and NAT2[J]. Biochem J, 2000, 348(1):159-166.
[13] 朱志远, 袁靖, 李金恒.人类N -乙酰化酶2 蛋白质三维结构的计算机模拟技术的研究进展[J].中国药理学通报, 2008, 24(11):1261-1264.
[14] Janin J, Henrick K, Moult J, et al.CAPRI:a critical assessment of predicted interactions[J].Proteins, 2003, 52(1):2-9.
[15] Smith GR, Sternberg MJE, Bates PA.The relationship between the flexibility of proteins and their conformational states on forming protein-protein complexes with application to protein-protein docking[J].Mol Biol, 2005, 347(5):1077-1101.
[16] Aloy P, Querol E, Aviles FX, et al.Automated structure based prediction of functional sites in proteins:applications to assessing the validity of inheriting protein function from homology in genome annotation and to protein docking[J].Mol Biol, 2001, 311(2):395-408.
[17] 乔圆圆, 郭盛.分子模拟软件MOE 及其在药物发现中的应用示例[J].计算机与应用化学, 2005, 22(2):157-160.
[18] 何谷, 黄文才, 郭丽.CCK1 受体的同源模拟和分子对接研究[J].化学学报, 2008, 66(3):97-103.
[19] 陈冰, 李金恒, 黄晶, 等.一步等位基因特异扩增法检测中国人N-乙酰化酶2[J].中国临床药理学杂志, 2004, 20(11):49-52.
[20] Ma XH, Li CH, Shen LZ, et al.Biologically-enhanced sampling geometric docking and backbone flexibility treatment with multi-conformational superposition[J].Proteins, 2005, 60(2):319-323.
[21] Wang C, Schueler-Furman O, Baker D.Improved sidechain modeling for protein-protein docking[J].Prot Sci, 2005, 14(9):1328-1339.
[22] Sinclair JC, Sandy J, Delgoda R, et al.Structure of arylamine Nat2-acetyltransferase reveals a catalytic triad[J]. Nat Struct Biol, 2000, 7(6):560-564.
[23] Nikolich Zugich J, SlifkaMK, Messaoudi I.The many important facets of Tcell repertoire diversity[J].Nat Rev Im-munol, 2004, 4(11):123-132.
[24] Peter TG, Karl BM.Transferrin:structure, function and potential therapeutic actions[J]. Drug Discov Today, 2005, 10(2):267-273.
[25] Henry L, Narendra PS.Oral artemisinin prevents and delays the development of 7, 12-dimethylbenz[a ] anthracene (DMBA)-induced breast cancer in the rat[J].Cancer Lett, 2006, 231(16):43-48.
[26] 柳乃方, 屈凌波, 相秉仁, 等.青蒿素类化合物抗肿瘤机制研究-青蒿素类化合物转铁蛋白对接研究[J].药学学报, 2009, 44(2):140-144.
[27] Ikuhiko N, Henry L, Narendra PS, et al.Anticancer properties of artemisinin derivatives and their targeted delivery by transferrin conjugation[J].Int J Pharm, 2007, 9(6):3-9.
[28] 李金恒. 临床个体化用药中的药物基因组学考虑[J].中国临床药理学与治疗学, 2007, 12(4):371-375.