生物大分子多尺度理论和计算方法

李文飞; 张建; 王骏; 王炜

doi:10.7498/aps.64.098701

摘要

分子模拟是研究生物大分子的重要手段. 过去二十年来, 人们将分子模拟与实验研究相结合, 揭示出生物大分子结构和动力学方面的诸多重要性质. 传统分子模拟主要采用全原子分子模型或各种粗粒化的分子模型. 在实际应用中, 传统分子模拟方法通常存在精度或效率瓶颈, 一定程度上限制了其应用范围. 近年来, 多尺度分子模型越来越受到人们的关注. 多尺度分子模型基于统计力学原理, 将全原子模型和粗粒化模型相耦合, 有望克服传统分子模拟方法中的精度/效率瓶颈, 进而拓展分子模拟在生物大分子研究中的应用范围. 根据模型之间的耦合方式, 近年来发展起来的多尺度分子模拟方法可归纳为如下四种类型: 混合分辨多尺度模型、并行耦合多尺度模型、单向耦合多尺度模型、以及自学习多尺度模型. 本文将对上述四类多尺度模型做简要介绍, 并讨论其主要优缺点、应用范围以及进一步发展方向.

关键词:

Abstract

Molecular simulation is one of the most important ways of studying biomolecules. In the last two decades, by combining the molecular simulations with experiments, a number of key features of structure and dynamics of biomolecules have been reflealed. Traditional molecular simulations often use the all-atom model or some coarse grained models. In practical applications, however, these all-atom models and coarse grained models encounter the bottlenecks in accuracy and efficiency, respectively, which hinder their applications to some extent. In reflent years, the multiscale models have attracted much attention in the field of biomolecule simulations. In the multiscale model, the atomistic models and coarse grained models are combined together based on the principle of statistical physics, and thus the bottlenecks encountered in the traditional models can be overcome. The currently available multiscale models can be classified into four categories according to the coupling ways between the all-atom model and coarse gained model. They are 1) hybrid resolution multiscale model, 2) parallel coupling multiscale model, 3) one-way coupling multiscale model, and 4) self-learning multiscale model. All these multiscale strategies have achieved great success in certain aspects in the field of biomolecule simulations, including protein folding, aggregation, and functional motions of many kinds of protein machineries. In this review, we briefly introduce the above-mentioned four multiscale strategies, and the examples of their applications. We also discuss the limitations and advantages, as well as the application scopes of these multiscale methods. The directions for future work on improving these multiscale models are also suggested. Finally, a summary and some prospects are preflented.

Keywords:

作者及机构信息

1.
南京大学物理学院, 固体微结构国家实验室, 南京 210093;

2.
人工微结构科学与技术协同创新中心, 南京 210093

基金项目: 国家自然科学基金(批准号: 11174134, 11334004, 11274157, 11174133)和江苏省自然科学基金(批准号: BK2011546)资助的课题.

Authors and contacts

1.
National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing 210093, China;

2.
Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China

Funds: Project supported by the National Natural Science Foundation of China (Grant Nos. 11174134, 11334004, 11274157, 11174133), and the Natural Science Foundation of Jiangsu Province (Grant No. BK2011546).

参考文献

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[53]	Li W F, Wang W, Takada S 2014 Proc. Natl. Acad. Sci. USA 111 10550
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[57]	Thorpe I F, Zhou J, Voth G A 2008 J. Phys. Chem. B 112 13079
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[59]	Hori N, Takada S 2012 J. Chem. Theory Comput. 8 3384
[60]	Gohlke H, Kiel C, Case D A 2003 J. Mol. Biol. 330 891
[61]	Li W F, Wang J, Zhang J, Wang W 2014 Curr. Opin. Struct. Biol. 30 25
[62]	Terakawa T, Takada S 2011 Biophys. J. 101 1450
[63]	Bryngelson J D, Onuchic J N, Socci N D, Wolynes P G 1995 Proteins 21 167
[64]	Pirchi M, Ziv G, Riven I, Cohen SS, Zohar N, Barak Y, Haran G 2011 Nat. Commun. 2 493
[65]	King N P, Jacobitz A W, Sawaya M R, Goldschmidt L, Yeates T O 2010 Proc. Natl. Acad. Sci. USA 107 20732
[66]	Kenzaki H, Koga N, Hori N, Kanada R, Li W, Okazaki K I, Yao X Q, Takada S 1992 J. Chem. Theory Comput. 7 1979
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施引文献

[1]	Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P 2007 Molecular Biology of the Cell (1st Ed.) (New York: Garland Science, Taylor & Francis Group)
[2]	Abrahams J P, Leslie A G W, Lutter R, Walker J E 1994 Nature 370 621
[3]	Sun B, Wei K J, Zhang B, Zhang X H, Dou S X, Li M, Xi X G 2008 Embo. J. 27 3279
[4]	Glynn SE, Martin A, Nager AR, Baker TA, Sauer RT 2009 Cell 139 744
[5]	Stigler J, Ziegler F, Gieseke A, Gebhardt J C, Rief M 2011 Science 334 512
[6]	Lv C, Gao X, Li W, Xue B, Qin M, Burtnick L D, Zhou H, Cao Y, Robinson R C, Wang W 2014 Nat. Commun. 5 4623
[7]	Lindorff-Larsen K, Piana S, Dror RO, Shaw D E 2011 Science 334 517
[8]	Zhang J, Li W F, Wang J, Qin M, Wu L, Yan Z Q, Xu W X, Zuo G H, Wang W 2009 Iubmb Life 61 627
[9]	Levitt M, Warshel A 1975 Nature 253 694
[10]	Li W F, Zhang J, Wang J, Wang W 2008 J. Am. Chem. Soc. 130 892
[11]	Duan Y, Kollman P A 1998 Science 282 740
[12]	Zhao G P, Perilla J R, Yufenyuy E L, Meng X, Chen B, Ning J Y, Ahn J, Gronenborn A M, Schulten K, Aiken C 2013 Nature 497 643
[13]	Guo C, Luo Y, Zhou R H, Wei G H 2012 ACS Nano 6 3907
[14]	Xie L G, Luo Y, Lin D D, Xi W H, Yang X J, Wei G H 2014 Nanoscale 6 9752
[15]	He J B, Zhang Z Y, Shi Y Y, Liu H Y 2013 J. Chem. Phys. 119 4005
[16]	Li W F, Zhang J, Su Y, Wang J, Qin M, Wang W 2007 J. Phys. Chem. B 111 13814
[17]	Bian Y, Tan C, Wang J, Sheng Y, Zhang J, Wang W 2014 PLoS Comput. Biol. 10 e1003562
[18]	Inanami T, Terada T P, Sasai M 2014 Proc. Natl. Acad. Sci. USA. 111 15969
[19]	Huang Y D, Shuai J W 2013 J. Phys. Chem. B 7 11
[20]	Takada S 2012 Curr. Opin. Struct. Biol. 22 130
[21]	Vendruscolo M, Dobson CM 2011 Current Biology 21 R68
[22]	Tozzini V 2010 Q. Rev. Biophys. 43 333
[23]	Tozzini V 2005 Curr. Opin. Struc. Biol. 15 144
[24]	Xu W X, Lai Z Z, Oliveira R J, Leite V B P, Wang J 2012 J. Phys. Chem. B 116 5152
[25]	Yao X Q, Kenzaki H, Murakami S, Takada S 2010 Nature Commun. 1 1116
[26]	Moritsugu K, Smith J C 2007 Biophys. J. 93 3460
[27]	Marrink S J, Risselada H J, Yefimov S, Tieleman D P, de Vries A H 2007 J. Phys. Chem. B 111 7812
[28]	Zuo G H, Wang J, Wang W 2006 Proteins 63 165
[29]	Koga N, Takada S 2001 J. Mol. Biol. 313 171
[30]	Clementi C, Nymeyer H, Onuchic J N 2000 J. Mol. Biol. 298 937
[31]	Onuchic J N, Luthey-Schulten Z, Wolynes P G 1997 Annu. Rev. Phys. Chem. 48 545
[32]	Go N 1983 Annu. Rev. Biophys. Bioeng. 12 183
[33]	Zhou H X 2014 Curr. Opin. Struct. Biol. 25 67
[34]	Li W F, Yoshii H, Hori N, Kameda T, Takada S 2010 Methods 52 106
[35]	Li W F, Takada S 2010 Biophys. J. 99 3029
[36]	Li WF, Takada S 2009 J. Chem. Phys. 130 214108
[37]	Praprotnik M, Delle Site L, Krefler K 2008 Annu. Rev Phys. Chem. 59 545
[38]	Liu P, Shi Q, Lyman E, Voth G A 2008 J. Chem. Phys. 129 114103
[39]	Liu P, Voth G A 2007 J. Chem. Phys. 126 045106
[40]	Chu J W, Ayton G S, Izvekov S, Voth G 2007 Mol. Phys. 105 167
[41]	Lyman E, Zuckerman D M 2006 J. Chem. Theory Comput. 2 656
[42]	Lyman E, Ytreflerg F M, Zuckerman D M 2006 Phys. Rev. Lett. 96 028105
[43]	Christen M, van Gunsteren W F 2006 J. Chem. Phys. 124 154106
[44]	Neri M, Anselmi C, Cascella M, Maritan A, Carloni P 2005 Phys. Rev. Lett. 95 218102
[45]	Lwin T Z, Luo R 2005 J. Chem. Phys. 123 194904
[46]	Izvekov S, Voth G A 2005 J. Phys. Chem. B 109 2469
[47]	Reith D, Putz M, Muller-Plathe F 2003 J. Comput. Chem. 24 1624
[48]	Peter C, Krefler K 2010 Faraday Discuss 144 9
[49]	Peter C, Krefler K 2009 Soft Matter 5 4357
[50]	Praprotnik M, Delle Site L, Krefler K J. Chem. Phys. 123 224106
[51]	Moritsugu K, Terada T, Kidera A 2010 J. Chem. Phys. 133 224105
[52]	Moritsugu K, Terada T, Kidera A 2012 J. Am. Chem. Soc. 134 7094
[53]	Li W F, Wang W, Takada S 2014 Proc. Natl. Acad. Sci. USA 111 10550
[54]	Li W F, Terakawa T, Wang W, Takada S 2012 Proc. Natl. Acad. Sci. USA 109 17789
[55]	Li W F, Wolynes P G, Takada S 2011 Proc. Natl. Acad. Sci. USA 108 3504
[56]	Warshel A, Levitt M 1976 J. Mol. Biol. 103 23
[57]	Thorpe I F, Zhou J, Voth G A 2008 J. Phys. Chem. B 112 13079
[58]	Trylska J, Tozzini V, McCammon J A 2005 Biophys. J. 89 1455
[59]	Hori N, Takada S 2012 J. Chem. Theory Comput. 8 3384
[60]	Gohlke H, Kiel C, Case D A 2003 J. Mol. Biol. 330 891
[61]	Li W F, Wang J, Zhang J, Wang W 2014 Curr. Opin. Struct. Biol. 30 25
[62]	Terakawa T, Takada S 2011 Biophys. J. 101 1450
[63]	Bryngelson J D, Onuchic J N, Socci N D, Wolynes P G 1995 Proteins 21 167
[64]	Pirchi M, Ziv G, Riven I, Cohen SS, Zohar N, Barak Y, Haran G 2011 Nat. Commun. 2 493
[65]	King N P, Jacobitz A W, Sawaya M R, Goldschmidt L, Yeates T O 2010 Proc. Natl. Acad. Sci. USA 107 20732
[66]	Kenzaki H, Koga N, Hori N, Kanada R, Li W, Okazaki K I, Yao X Q, Takada S 1992 J. Chem. Theory Comput. 7 1979
[67]	Kumar S, Bouzida D, Swendsen R H, Kollman P A, Rosenberg J M 2013 J. Comput. Chem. 13 1011
[68]	Heath A P, Kavraki L E, Clementi C 2007 Proteins 68 646
[69]	Gront D, Kmiecik S, Kolinski A 2007 J. Comput. Chem. 28 1593
[70]	Canutescu A A, Shelenkov A A, Dunbrack R L 2003 Protein Sci. 12 2001

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