English
往期目录
新闻公告
More
化学进展 2012, Vol. 24 Issue (06): 1175-1184 前一篇   后一篇

所属专题： 计算化学； 酶化学

• 量子化学专辑 •

锌酶的计算模拟:挑战与最新进展

巫瑞波1, 曹泽星*2, 张颖凯*3   

  1. 1. 中山大学药学院 广州 510006;
    2. 厦门大学化学化工学院福建省理论与计算化学 重点实验室 厦门 361005;
    3. 纽约大学化学系 纽约 10003
  • 收稿日期:2011-11-01 修回日期:2012-03-01 出版日期:2012-06-24 发布日期:2012-05-11
  • 通讯作者: 曹泽星, 张颖凯 E-mail:zxcao@xmu.edu.cn;yz22@nyu.edu
  • 基金资助:

    国家重点基础研究发展计划(973)项目(No.2011CB808504和2012CB214902)和国家自然科学基金项目(No.2133007和20873105)资助

下载PDF ( 1270 ) 引用
导出 被引次数 ( 1 )

Computational Simulations of Zinc Enzyme: Challenges and Recent Advances

Wu Ruibo1, Cao Zexing2, Zhang Yingkai3   

  1. 1. School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China;
    2. College of Chemistry and Chemical Engineering, Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, Xiamen University, Xiamen 361005, China;
    3. Department of Chemistry, New York University, New York 10003, US
  • Received:2011-11-01 Revised:2012-03-01 Online:2012-06-24 Published:2012-05-11
锌酶在人体中分布非常广泛,种类繁多,是当前最受关注的金属酶之一。由于在锌配位结构上的多样性以及Zn2+饱和的d轨道带来的“光谱寂静”性,导致许多实验研究手段受限。计算模拟在锌酶的研究中发挥着越来越重要的作用,已经成为不可或缺的研究工具。现代量子化学计算模拟方法,特别是被视为研究生物大分子体系非常有效的QM/MM组合方法,目前已经被广泛应用于探讨复杂多变的锌配位结构以及锌酶催化反应机理。通过在QM/MM水平下开展的分子动力学模拟,可以揭示锌酶体系中结构与功能间的相互关系。此外,分子力场方法在锌酶研究中同样发挥了不可替代的作用,由于传统力场普遍无法正确描述锌配位结构,因此,锌酶分子力场的开发具有迫切的现实意义。本文总结了近年来锌酶计算模拟领域的最新进展,提出了锌酶计算研究中还有待解决的一些问题。
关键词： 锌酶, 量子力学/分子力学组合方法, 分子动力学模拟, 力场, 反应机理, 配位结构
Zinc enzymes play a variety of essential biological roles, and their functions and/or structural organizations are critically dependent on the zinc binding site. However, the zinc coordination shell is so complicated that an accurate and powerful theoretical simulation protocol is highly required in calculation. Herein, we review the recent studies of the selected zinc enzymes by the state-of-the-art combined quantum mechanism/molecular mechanism molecular dynamics (QM/MM MD) simulations in probing the reaction mechanism and revealing the relationship of structure and function. Meanwhile, the accuracy of all the current available pairwise force fields to describe zinc coordination structure is very poor, so the recent development of force fields for zinc enzyme is also presented. By the end of this review, some prospects and suggestions are given for further exploration of zinc enzyme. 1 Significance and challenges of zinc enzymes
1.1 Zinc enzyme
1.2 Challenges of experimental research in zinc enzyme
1.3 Challenges of computational research in zinc enzym
2 Recent advance of computational research in zinc enzyme
2.1 QM/MM study of zinc enzyme
2.2 Force field development for zinc enzyme
3 Outlook
Key words: zinc enzyme, QM/MM, molecular dynamics simulation, force field, reaction mechanism, coordination geometry Contents

中图分类号: 

()
[1] Andreini C, Banci L, Bertini I, Rosato A. J. Proteome Res., 2006, 5: 196-201
[2] Auld D S. Biometals, 2001, 14: 271-313
[3] Anzellotti A I, Farrell N P. Chem. Soc. Rev., 2008, 37: 1629-1651
[4] Parkin G. Chem. Rev., 2004, 104: 699-767
[5] Maret W, Li Y. Chem. Rev., 2009, 109: 4682-707
[6] Shankar S, Srivastava R K. Programmed Cell Death in Cancer Progression and Therapy, 2008, 615: 261-298
[7] Mueller S, Kraemer O H. Curr. Cancer Drug Tar., 2010, 10: 210-228
[8] Li X, Wu J F. Recent Patents on Anti-Cancer Drug Discovery, 2010, 5: 109-141
[9] Bourboulia D, Stetler-Stevenson W G. Seminars in Cancer Biology, 2010, 20: 161-168
[10] Ropero S, Esteller M. Molecular Oncology, 2007, 1: 19-25
[11] Parkin G. Chem. Comm., 2000, 1971-1985
[12] Yi L, Yeung N, Sieracki N, Marshall N M. Nature, 2009, 855-62
[13] Bock C W, Katz A K, Glusker J P. J. Am. Chem. Soc., 1995, 117: 3754-3763
[14] Sigel H, Martin R B. Chem. Soc. Rev., 1994, 23: 83-91
[15] Cook J D, Penner-Hahn J E, Stemmler T L. Methods in Nano Cell Biology, 2008, 90: 199-216
[16] Somoza J R, Skene R J, Katz B A, Mol C, Ho J D, Jennings A J, Luong C, Arvai A, Buggy J J, Chi E, Tang J, Sang B C, Verner E, Wynands R, Leahy E M, Dougan D R, Snell G, Navre M, Knuth M W, Swanson R V, McRee D E, Tari L W. Structure, 2004, 12: 1325-1334
[17] Schuetz A, Min J, Allali-Hassani A, Schapira M, Shuen M, Loppnau P, Mazitschek R, Kwiatkowski N P, Lewis T A, Maglathin R L, McLean T H, Bochkarev A, Plotnikov A N, Vedadi M, Arrowsmith C H. J. Biol. Chem., 2008, 283: 11355-11363
[18] Bottomley M J, Lo Surdo P, Di Giovine P, Cirillo A, Scarpelli R, Ferrigno F, Jones P, Neddermann P, De Francesco R, Steinkuhler C, Gallinari P, Carfi A. J. Biol. Chem., 2008, 283: 26694-26704
[19] Wu R B, Hu P, Wang S L, Cao Z X, Zhang Y K. J. Chem. Theory Comput., 2010, 6: 337-343
[20] Li Y L, Mei Y, Zhang D W, Xie D Q, Zhang J Z H. J. Phys. Chem. B, 2011, 115: 10154-10162
[21] Lipton A S, Heck R W, Staeheli G R, Valiev M, De Jong W A, Ellis P D. J. Am. Chem. Soc., 2008, 130: 6224-6230
[22] Ressalan S, Iyer C S P. Rev. Anal. Chem., 2004, 23: 159-232
[23] Tamames B, Sousa S F, Tamames J, Fernandes P A, Ramos M J. Proteins: Struct., Funct., Bioinf., 2007, 69: 466-475
[24] Ramos M J, Fernandes P A. Accounts Chem. Res., 2008, 41: 689-698
[25] Kraut D A, Carroll K S, Herschlag D. Annu. Rev. of Biochem., 2003, 72: 517-571
[26] Khandelwal A, Lukacova V, Comez D, Kroll D M, Raha S, Balaz S. J. Med. Chem., 2005, 48: 5437-5447
[27] Irwin J J, Raushel F M, Shoichet B K. Biochemistry, 2005, 44: 12316-12328
[28] Gao H, Ke Z, DeYonker N J, Wang J, Xu H, Mao Z W, Phillips D L, Zhao C. J. Am. Chem. Soc., 2011, 133: 2904-2915
[29] Himo F. Theor. Chem. Acc., 2006, 116: 232-240
[30] Senn H M, Thiel W. Angew. Chem., 2009, 48: 1198-1229
[31] Hu H, Yang W T. J. Mol. Struc-Theochem, 2009, 898: 17-30
[32] Acevedo O, Jorgensen W L. Acc. Chem. Res., 2010, 43: 142-151
[33] Ranaghan K E, Mulholland A. J. Int. Rev. Phys. Chem., 2010, 29: 65-133
[34] Wu R, Lu Z, Cao Z, Zhang Y. J. Am. Chem. Soc., 2011, 133: 6110-6113
[35] Wu R, Wang S, Zhou N, Cao Z, Zhang Y. J. Am. Chem. Soc., 2010, 132: 9471-9479
[36] Blumberger J, Lamoureux G, Klein M L. J. Chem. Theory Comput., 2007, 3: 1837-1850
[37] Zhang X, Wu R, Song L, Lin Y, Lin M, Cao Z, Wu W, Mo Y. J. Comput. Chem., 2009, 30: 2388-2401
[38] Wu R, Xie H, Mo Y, Cao Z. J. Phys. Chem. A, 2009, 113: 11595-11603
[39] Wu R, Xie H, Cao Z, Mo Y. J. Am. Chem. Soc., 2008, 130: 7022-7031
[40] Wong K Y, Gao J. Biochemistry, 2007, 46: 13352-13369
[41] Riccardi D, Yang S, Cui Q. BBA-Proteins and Proteomics, 2010, 1804: 342-351
[42] Yang X J, Seto E. Oncogene, 2007, 26: 5310-5318
[43] Wang D F, Helquist P, Wiest O. J. Org. Chem., 2007, 72: 5446-5449
[44] Bradner J E, West N, Grachan M L, Greenberg E F, Haggarty S J, Warnow T, Mazitschek R. Nat. Chem. Biol., 2010, 6: 238-243
[45] Menikarachchi L C, Gascon J A. Curr. Top. Med. Chem., 2010, 10: 46-54
[46] Cho A E, Rinaldo D. J. Comput. Chem., 2009, 30: 2609-2616
[47] Khandelwal A, Balaz S. J. Comput. Aid. Mol. Des., 2007, 21: 131-137
[48] Khandelwal A, Balaz S. Proteins: Struct., Funct., Bioinf., 2007, 69: 326-339
[49] Lamoureux G, Blumberger J, Klein M L. Abstracts of Papers of the American Chemical Society, 2006, 232: 256-256
[50] Wong K Y, Gao J. Febs Journal, 2011, 278: 2579-2595
[51] Xiong Y, Lu H T, Zhan C G. J. Comput. Chem., 2008, 29: 1259-1267
[52] Lopez-Canut V, Roca M, Bertran J, Moliner V, Tunon I. J. Am. Chem. Soc., 2011, 133: 12050-12062
[53] Klusak V, Barinka C, Plechanovova A, Mlcochova P, Konvalinka J, Rulisek L, Lubkowski J. Biochemistry, 2009, 48: 4126-4138
[54] Szeto M W Y, Mujika J I, Zurek J, Mulholland A J, Harvey J N. J. Mol. Struc-Theochem, 2009, 898: 106-114
[55] Schurer G, Lanig H, Clark T. Biochemistry, 2004, 43: 5414-5427
[56] Ho M H, De Vivo M, Dal Peraro M, Klein M L. J. Chem. Theory Comput., 2009, 5: 1657-1666
[57] Riccardi D, Koenig P, Guo H, Cui Q. Biochemistry, 2008, 47: 2369-2378
[58] Wu S S, Xu D G, Guo H. J. Am. Chem. Soc., 2010, 132: 17986-17988
[59] Xiao C, Zhang Y. J. Phys. Chem. B, 2007, 111: 6229-6235
[60] Yao L, Yan H, Cukier R I. J. Phys. Chem. B, 2006, 110: 26320-26326
[61] Riccardi D, Cui Q. J. Phys. Chem. A, 2007, 111: 5703-5711
[62] Li X, Hayik S A, Merz K M Jr. J. Inorg. Biochem., 2010, 104: 512-522
[63] Hoops S C, Anderson K W, Merz K M Jr. J. Am. Chem. Soc., 1991, 113: 8262-8270
[64] Bredenberg J, Nilsson L. Int. J. Quantum Chem., 2001, 83: 230-244
[65] Li W, Zhang J, Wang J, Wang W. J. Am. Chem. Soc., 2008, 130: 892-900
[66] Stote R H, Karplus M. Proteins: Struct., Funct., Genet., 1995, 23: 12-31
[67] Zimmer M. Coord. Chem. Rev., 2009, 253: 817-826
[68] Pang Y P. Proteins: Struct., Funct., Genet., 2001, 45: 183-189
[69] Peters M B, Yang Y, Wang B, Fuesti-Molnar L, Weaver M N, Merz K M Jr. J. Chem. Theory Comput., 2010, 6: 2935-2947
[70] Lin F, Wang R. J. Chem. Theory Comput., 2010, 6: 1852-1870
[71] Sakharov D V, Lim C. J. Comput. Chem., 2009, 30: 191-202
[72] Wu R, Lu Z, Cao Z, Zhang Y. J. Chem. Theory Comput., 2011, 7: 433-443
[73] Gresh N, Piquemal J P, Krauss M. J. Comput. Chem., 2005, 26: 1113-1130
[74] Zhang Y, Lin H. Theor. Chem. Acc., 2010, 126: 315-322
[75] Zhang Y, Lin H J. Chem. Theory Comput., 2008, 4: 414-425
[76] Pezeshki S, Lin H. J. Chem. Theory Comput., 2011, 7, 3625-3634
[77] Kerdcharoen T, Morokuma K. Chemical Physics Letters, 2002, 355: 257-262
[78] Warshel A, Kato M, Pisliakov A V. J. Chem. Theory Comput., 2007, 3: 2034-2045
[79] Jorgensen W L. J. Chem. Theory Comput., 2007, 3: 1877-1877
[1] 贾斌, 刘晓磊, 刘志明. 贵金属催化剂上氢气选择性催化还原NOx[J]. 化学进展, 2022, 34(8): 1678-1687.
[2] 张明珏, 凡长坡, 王龙, 吴雪静, 周瑜, 王军. 以双氧水或氧气为氧化剂的苯羟基化制苯酚的催化反应机理[J]. 化学进展, 2022, 34(5): 1026-1041.
[3] 张柏林, 张生杨, 张深根. 稀土元素在脱硝催化剂中的应用[J]. 化学进展, 2022, 34(2): 301-318.
[4] 白文己, 石宇冰, 母伟花, 李江平, 于嘉玮. Cs2CO3辅助钯催化X—H (X=C、O、N、B)官能团化反应的理论计算研究[J]. 化学进展, 2022, 34(10): 2283-2301.
[5] 王学川, 王岩松, 韩庆鑫, 孙晓龙. 有机小分子荧光探针对甲醛的识别及其应用[J]. 化学进展, 2021, 33(9): 1496-1510.
[6] 张维佳, 邵学广, 蔡文生. 抗冻蛋白抗冻机制的分子模拟研究[J]. 化学进展, 2021, 33(10): 1797-1811.
[7] 徐昌藩, 房鑫, 湛菁, 陈佳希, 梁风. 金属-二氧化碳电池的发展:机理及关键材料[J]. 化学进展, 2020, 32(6): 836-850.
[8] 刘玥, 吴忆涵, 庞宏伟, 王祥学, 于淑君, 王祥科. 石墨相氮化碳材料在水环境污染物去除中的研究[J]. 化学进展, 2019, 31(6): 831-846.
[9] 陈淏川, 付浩浩, 邵学广, 蔡文生. 重要性采样方法与自由能计算[J]. 化学进展, 2018, 30(7): 921-931.
[10] 葛明, 李振路. 基于银系半导体材料的全固态Z型光催化体系[J]. 化学进展, 2017, 29(8): 846-858.
[11] 沈晓骏, 黄攀丽, 文甲龙, 孙润仓. 木质素氧化还原解聚研究现状[J]. 化学进展, 2017, 29(1): 162-178.
[12] 姚臻, 戴博恩, 于云飞, 曹堃. 巯基-环氧点击化学及其在高分子材料中的应用[J]. 化学进展, 2016, 28(7): 1062-1069.
[13] 赵艳霞, 何圣贵. 异核氧化物团簇与小分子的反应研究[J]. 化学进展, 2016, 28(4): 401-414.
[14] 花东龙, 庄晓煜, 童东绅, 俞卫华, 周春晖. 催化甘油脱水氧化连串反应制丙烯酸[J]. 化学进展, 2016, 28(2/3): 375-390.
[15] 杨越, 刘琪英, 蔡炽柳, 谈金, 王铁军, 马隆龙. 木质纤维素催化转化制备DMF和C5/C6烷烃[J]. 化学进展, 2016, 28(2/3): 363-374.
阅读次数
全文


摘要

锌酶的计算模拟:挑战与最新进展