内禀无序蛋白构象与带电氨基酸残基排布关系——以精氨酸和天冬氨酸组成的随机多肽为例

康文斌; 王骏; 王炜

doi:10.7498/aps.67.20172246

摘要

内禀无序蛋白的结构特征与其氨基酸序列有着密切的联系.其中一个核心问题是正负带电氨基酸残基的排列如何影响无序蛋白或者多肽的构象?为了回答这一问题，本研究以天冬氨酸和精氨酸两种带电残基组成的随机多肽为研究对象，利用全原子蒙特卡罗模拟和温度副本交换采样方法，研究了随机多肽的电荷排布与结构之间的定性关系.结果表明：正负带电残基在序列上混合均匀时，由于肽链内部的静电吸引和排斥相互抵消，肽链倾向于形成无规卷曲的构象；正负带电残基分离时，由于长程静电相互吸引，多肽倾向于形成类β-发卡的形状.

关键词:

Abstract

The relationship between the sequential and structural features of intrinsically disordered peptides (IDPs) has attracted much attention during the recent decade. One essential problem relating to sequence-structure relationship is how the distribution of charged residues affects the structure of IDP. In this work, we address this problem with simulations on a series of random peptides composed of arginine and aspartic acids. With the ABSINTH implicit solvation model, the structural ensembles are generated with Markov Chain Monte Carlo method and replica-exchange sampling. The relations between various structural features (including the gyration radius, the tail distance, the distance between residues, and asphericity) and the distribution of charged residues are analyzed. Several limit cases (with parts of interactions switched off) are also calculated for comparison. The conversion from extended conformations to compact structures is observed, following the demixing of negatively and positively charged residues along the sequence. For the cases with well-mixed charges, the intra-chain electrostatic repulsions and attractions are balanced, which results in a generic Flory random coil-like conformation. Differently, for the case with well-separated charged residues, the electrostatic attraction between residues distant along the sequence induces a semi-compact hairpin-like conformation. This is consistent with the observations of Pappu group. Our results suggest that the structural dependence on charge distribution would not be sensitive to the selection of amino acid, and is determined by the patterns of charges, which demonstrates the robustness of the mechanism that the charge distribution modulates the structural features in the IDP system. Our results may broaden our understanding of the sequence-structure relation of IDP system.

Keywords:

作者及机构信息

1.
南京大学物理学院, 南京 210093;

2.
湖北医药学院数理教研室, 十堰 442000;

3.
湖北医药学院Bio-X研究中心, 十堰 442000

通信作者: 康文斌, wbkang@hbmu.edu.cn;wangj@nju.edu.cn;wangwei@nju.edu.cn ; 王骏, wbkang@hbmu.edu.cn;wangj@nju.edu.cn;wangwei@nju.edu.cn ; 王炜, wbkang@hbmu.edu.cn;wangj@nju.edu.cn;wangwei@nju.edu.cn

基金项目: 国家重点基础研究发展计划（批准号：2013CB834100）、国家自然科学基金（批准号：11334004，11174133，81421091，11774157）、2017年国家级大学生创新创业训练计划（批准号：201710929002）和湖北医药学院研究生启动金（批准号：2011QDZR-11）资助的课题.

Authors and contacts

1.
School of Physics, Nanjing University, Nanjing 210093, China;

2.
Department of Mathematics and Physics, Hubei University of Medicine, Shiyan 442000, China;

3.
Bio-X Research Center, Hubei University of Medicine, Shiyan 442000, China

Corresponding author: Kang Wen-Bin, wbkang@hbmu.edu.cn;wangj@nju.edu.cn;wangwei@nju.edu.cn ; Wang Jun, wbkang@hbmu.edu.cn;wangj@nju.edu.cn;wangwei@nju.edu.cn ; Wang Wei, wbkang@hbmu.edu.cn;wangj@nju.edu.cn;wangwei@nju.edu.cn

Funds: Project supported by the National Basic Research Program of China (Grant No. 2013CB834100), the National Natural Science Foundation of China (Grant Nos. 11334004, 11174133, 81421091, 11774157), the 2017 National Training Program of Innovation and Entrepreneurship for Undergraduates, China (Grant No. 201710929002), and the Initial Project for Post-Graduates of Hubei University of Medicine, China (Grant No. 2011QDZR-11).

参考文献

[1]	Tantos A, Han K H, Tompa P 2012 Mol. Cell. Endocrinol. 348 457
[2]	Dyson H J, Wright P E 2005 Nat. Rev. Mol. Cell Biol. 6 197
[3]	Uversky V N 2002 Eur. J. Biochem. 69 2
[4]	Das R K, Pappu R V 2013 Proc. Natl. Acad. Sci. USA 110 13392
[5]	Yu J F, Dou X H, Sha Y J, Wang C L, Wang H B, Chen Y T, Zhang F, Zhou Y, Wang J H 2017 BMC Bioinform. 18 206
[6]	Piovesan D, Tabaro F, Micetic I, et al. 2017 Nucl. Acids Res. 45 D1123
[7]	Potenza E, Di Domenico T, Walsh I, Tosatto S C 2015 Nucl. Acids Res. 43 D315
[8]	Varadi M, Kosol S, Lebrun P, Valentini E, Blackledge M, Dunker A K, Felli I C, Forman-Kay J D, Kriwacki R W, Pierattelli R, Sussman J, Svergun D I, Uversky V N, Vendruscolo M, Wishart D, Wright P E, Tompa P 2014 Nucl. Acids Res. 42 D326
[9]	Sickmeier M, Hamilton J A, LeGall T, Vacic V, Cortese M S, Tantos A, Szabo B, Tompa P, Chen J, Uversky V N, Obradovic Z, Dunker A K 2007 Nucl. Acids Res. 35 D786
[10]	Sim K L, Uchida T, Miyano S 2001 Bioinformatics 17 379
[11]	Forbes J G, Jin A J, Ma K, Gutierrez-Cruz G, Tsai W L, Wang K 2005 J. Muscle Res. Cell Motil. 26 291
[12]	Uversky V N 2002 Protein Sci. 11 739
[13]	Mao A H, Crick S L, Vitalis A, Chicoine C L, Pappu R V 2010 Proc. Natl. Acad. Sci. USA 107 8183
[14]	Kumar S, Hoh J H 2004 Biochem. Biophys. Res. Commun. 324 489
[15]	Hendus-Altenburger R, Lambrughi M, Terkelsen T, Pedersen S F, Papaleo E, Lindorff-Larsen K, Kragelund B B 2017 Cell. Signal 37 40
[16]	Malka-Gibor E, Kornreich M, Laser-Azogui A, Doron O, Zingerman-Koladko I, Harapin J, Medalia O, Beck R 2017 Biophys. J. 112 892
[17]	Khan S H, McLaughlin W A, Kumar R 2017 Sci. Rep. 7 15440
[18]	Lousa P, Nedozralova H, Zupa E, Novacek J, Hritz J 2017 Biophys. Chem. 223 25
[19]	Stakkestad O, Lyngstadaas S P, Thiede B, Vondrasek J, Skalhegg B S, Reseland J E 2017 Front. Physiol. 8 531
[20]	Liu J J, Dai J, He J F, Niemi A J, Ilieva N 2017 Phys. Rev. E 95 032406
[21]	Das R K, Huang Y, Phillips A H, Kriwacki R W, Pappu R V 2016 Proc. Natl. Acad. Sci. USA 113 5616
[22]	Lange J, Wyrwicz L S, Vriend G 2016 Bioinformatics 32 932
[23]	Arya S, Mukhopadhyay S 2014 J. Phys. Chem. B 118 9191
[24]	Kister A E, Potapov V 2013 Biochem. Soc. Trans. 41 616
[25]	Hoang T X, Trovato A, Seno F, Banavar J R, Maritan A 2012 Phys. Rev. E 86 050901
[26]	Huang Y Q, Liu Z R 2010 Acta Phys. Chim. Sin. 26 2061 (in Chinese) [黄永棋, 刘志荣 2010 物理化学学报 26 2061]
[27]	Dunker A K, Lawson J D, Brown C J, Williams R M, Romero P, Oh J S, Oldfield C J, Campen A M, Ratliff C M, Hipps K W, Ausio J, Nissen M S, Reeves R, Kang C, Kissinger C R, Bailey R W, Griswold M D, Chiu W, Garner E C, Obradovic Z 2001 J. Mol. Graph. Model. 19 26
[28]	Wang J, Wang W 1999 Nat. Struct. Biol. 6 1033
[29]	Li W F, Qin M, Tie Z X, Wang W 2011 Phys. Rev. E 84 041933
[30]	Wang J, Wang W 2016 Adv. Phys. X 1 444
[31]	Vitalis A, Pappu R V 2009 Annu. Rep. Comput. Chem. 5 49
[32]	Vitalis A, Pappu R V 2009 J. Comput. Chem. 30 673
[33]	Pappu R V, Wang X, Vitalis A, Crick S L 2008 Arch. Biochem. Biophys. 469 132
[34]	Cragnell C, Durand D, Cabane B, Skepo M 2016 Proteins 84 777
[35]	Venditto J G, Wolf S, Curotto E, Mella M 2015 Chem. Phys. Lett. 635 127
[36]	Wu H H, Chen C C, Chen C M 2012 J. Comput. Aided Mol. Des. 26 363
[37]	Liu Y, Kellogg E, Liang H J 2012 J. Chem. Phys. 137 045103
[38]	Odriozola G, Berthier L 2011 J. Chem. Phys. 134 054504
[39]	Turner C H, Brennan J K, Lisal M 2007 J. Phys. Chem. C 111 15706
[40]	Kokubo H, Okamoto Y 2004 J. Chem. Phys. 120 10837
[41]	Nakazawa T, Ban S, Okuda Y, Masuya M, Mitsutake A, Okamoto Y 2002 Biopolymers 63 273
[42]	Uversky V N 2013 Intrinsically Disordered Proteins 1 e24684
[43]	Childers M C, Towse C L, Daggett V 2016 Protein Eng. Des. Sel. 29 271
[44]	Yu C, Niu X, Jin F, Liu Z, Jin C, Lai L 2016 Sci. Rep. 6 22298
[45]	Guharoy M, Bhowmick P, Tompa P 2016 J. Biol. Chem. 291 6723
[46]	Nagibina G S, Tin U F, Glukhov A S, Melnik T N, Melnik B S 2016 Protein Pept. Lett. 23 176
[47]	Noivirt-Brik O, Horovitz A, Unger R 2009 PLoS Comput. Biol. 5 e1000592
[48]	Cheng Y, LeGall T, Oldfield C J, Mueller J P, Van Y Y, Romero P, Cortese M S, Uversky V N, Dunker A K 2006 Trends Biotechnol. 24 435
[49]	Ambroggio X I, Kuhlman B 2006 Curr. Opin. Struct. Biol. 16 525
[50]	Meng G Z 1986 Prog. Biochem. Biophys. 13 3 (in Chinese) [盂广震 1986 生物化学与生物物理进展 13 3]
[51]	Wang D C 2008 Protein Engineering (Vol. 1) (Beijing: Chemical Industry Press) p65 (in Chinese) [王大成 2008 蛋白质工程 (北京: 化学工业出版社) 第65页]
[52]	Deng H Y, Jia Y, Zhang Y 2016 Acta Phys. Sin. 65 178701 (in Chinese) [邓海游, 贾亚, 张阳 2016 物理学报 65 178701]

施引文献

[1]	Tantos A, Han K H, Tompa P 2012 Mol. Cell. Endocrinol. 348 457
[2]	Dyson H J, Wright P E 2005 Nat. Rev. Mol. Cell Biol. 6 197
[3]	Uversky V N 2002 Eur. J. Biochem. 69 2
[4]	Das R K, Pappu R V 2013 Proc. Natl. Acad. Sci. USA 110 13392
[5]	Yu J F, Dou X H, Sha Y J, Wang C L, Wang H B, Chen Y T, Zhang F, Zhou Y, Wang J H 2017 BMC Bioinform. 18 206
[6]	Piovesan D, Tabaro F, Micetic I, et al. 2017 Nucl. Acids Res. 45 D1123
[7]	Potenza E, Di Domenico T, Walsh I, Tosatto S C 2015 Nucl. Acids Res. 43 D315
[8]	Varadi M, Kosol S, Lebrun P, Valentini E, Blackledge M, Dunker A K, Felli I C, Forman-Kay J D, Kriwacki R W, Pierattelli R, Sussman J, Svergun D I, Uversky V N, Vendruscolo M, Wishart D, Wright P E, Tompa P 2014 Nucl. Acids Res. 42 D326
[9]	Sickmeier M, Hamilton J A, LeGall T, Vacic V, Cortese M S, Tantos A, Szabo B, Tompa P, Chen J, Uversky V N, Obradovic Z, Dunker A K 2007 Nucl. Acids Res. 35 D786
[10]	Sim K L, Uchida T, Miyano S 2001 Bioinformatics 17 379
[11]	Forbes J G, Jin A J, Ma K, Gutierrez-Cruz G, Tsai W L, Wang K 2005 J. Muscle Res. Cell Motil. 26 291
[12]	Uversky V N 2002 Protein Sci. 11 739
[13]	Mao A H, Crick S L, Vitalis A, Chicoine C L, Pappu R V 2010 Proc. Natl. Acad. Sci. USA 107 8183
[14]	Kumar S, Hoh J H 2004 Biochem. Biophys. Res. Commun. 324 489
[15]	Hendus-Altenburger R, Lambrughi M, Terkelsen T, Pedersen S F, Papaleo E, Lindorff-Larsen K, Kragelund B B 2017 Cell. Signal 37 40
[16]	Malka-Gibor E, Kornreich M, Laser-Azogui A, Doron O, Zingerman-Koladko I, Harapin J, Medalia O, Beck R 2017 Biophys. J. 112 892
[17]	Khan S H, McLaughlin W A, Kumar R 2017 Sci. Rep. 7 15440
[18]	Lousa P, Nedozralova H, Zupa E, Novacek J, Hritz J 2017 Biophys. Chem. 223 25
[19]	Stakkestad O, Lyngstadaas S P, Thiede B, Vondrasek J, Skalhegg B S, Reseland J E 2017 Front. Physiol. 8 531
[20]	Liu J J, Dai J, He J F, Niemi A J, Ilieva N 2017 Phys. Rev. E 95 032406
[21]	Das R K, Huang Y, Phillips A H, Kriwacki R W, Pappu R V 2016 Proc. Natl. Acad. Sci. USA 113 5616
[22]	Lange J, Wyrwicz L S, Vriend G 2016 Bioinformatics 32 932
[23]	Arya S, Mukhopadhyay S 2014 J. Phys. Chem. B 118 9191
[24]	Kister A E, Potapov V 2013 Biochem. Soc. Trans. 41 616
[25]	Hoang T X, Trovato A, Seno F, Banavar J R, Maritan A 2012 Phys. Rev. E 86 050901
[26]	Huang Y Q, Liu Z R 2010 Acta Phys. Chim. Sin. 26 2061 (in Chinese) [黄永棋, 刘志荣 2010 物理化学学报 26 2061]
[27]	Dunker A K, Lawson J D, Brown C J, Williams R M, Romero P, Oh J S, Oldfield C J, Campen A M, Ratliff C M, Hipps K W, Ausio J, Nissen M S, Reeves R, Kang C, Kissinger C R, Bailey R W, Griswold M D, Chiu W, Garner E C, Obradovic Z 2001 J. Mol. Graph. Model. 19 26
[28]	Wang J, Wang W 1999 Nat. Struct. Biol. 6 1033
[29]	Li W F, Qin M, Tie Z X, Wang W 2011 Phys. Rev. E 84 041933
[30]	Wang J, Wang W 2016 Adv. Phys. X 1 444
[31]	Vitalis A, Pappu R V 2009 Annu. Rep. Comput. Chem. 5 49
[32]	Vitalis A, Pappu R V 2009 J. Comput. Chem. 30 673
[33]	Pappu R V, Wang X, Vitalis A, Crick S L 2008 Arch. Biochem. Biophys. 469 132
[34]	Cragnell C, Durand D, Cabane B, Skepo M 2016 Proteins 84 777
[35]	Venditto J G, Wolf S, Curotto E, Mella M 2015 Chem. Phys. Lett. 635 127
[36]	Wu H H, Chen C C, Chen C M 2012 J. Comput. Aided Mol. Des. 26 363
[37]	Liu Y, Kellogg E, Liang H J 2012 J. Chem. Phys. 137 045103
[38]	Odriozola G, Berthier L 2011 J. Chem. Phys. 134 054504
[39]	Turner C H, Brennan J K, Lisal M 2007 J. Phys. Chem. C 111 15706
[40]	Kokubo H, Okamoto Y 2004 J. Chem. Phys. 120 10837
[41]	Nakazawa T, Ban S, Okuda Y, Masuya M, Mitsutake A, Okamoto Y 2002 Biopolymers 63 273
[42]	Uversky V N 2013 Intrinsically Disordered Proteins 1 e24684
[43]	Childers M C, Towse C L, Daggett V 2016 Protein Eng. Des. Sel. 29 271
[44]	Yu C, Niu X, Jin F, Liu Z, Jin C, Lai L 2016 Sci. Rep. 6 22298
[45]	Guharoy M, Bhowmick P, Tompa P 2016 J. Biol. Chem. 291 6723
[46]	Nagibina G S, Tin U F, Glukhov A S, Melnik T N, Melnik B S 2016 Protein Pept. Lett. 23 176
[47]	Noivirt-Brik O, Horovitz A, Unger R 2009 PLoS Comput. Biol. 5 e1000592
[48]	Cheng Y, LeGall T, Oldfield C J, Mueller J P, Van Y Y, Romero P, Cortese M S, Uversky V N, Dunker A K 2006 Trends Biotechnol. 24 435
[49]	Ambroggio X I, Kuhlman B 2006 Curr. Opin. Struct. Biol. 16 525
[50]	Meng G Z 1986 Prog. Biochem. Biophys. 13 3 (in Chinese) [盂广震 1986 生物化学与生物物理进展 13 3]
[51]	Wang D C 2008 Protein Engineering (Vol. 1) (Beijing: Chemical Industry Press) p65 (in Chinese) [王大成 2008 蛋白质工程 (北京: 化学工业出版社) 第65页]
[52]	Deng H Y, Jia Y, Zhang Y 2016 Acta Phys. Sin. 65 178701 (in Chinese) [邓海游, 贾亚, 张阳 2016 物理学报 65 178701]

[1]	刘乔, 黄家宸, 王昊, 邓亚骏. 前进接触线薄液膜结构与运移机制. 物理学报, 2024, 73(1): 016801. doi: 10.7498/aps.73.20231296
[2]	张雪松, 范振忠, 仝其雷, 付沅峰. 基于分子模拟方法的纳米气泡溃灭过程分析. 物理学报, 2024, 73(20): 204701. doi: 10.7498/aps.73.20241105
[3]	舒盼盼, 赵朋程, 王瑞. 110 GHz微波输出窗内表面次级电子倍增特性的电磁粒子模拟. 物理学报, 2023, 72(9): 095202. doi: 10.7498/aps.72.20222235
[4]	陈光临, 张志勇. 使用中间层受监督的自编码器探索蛋白质的构象空间. 物理学报, 2023, 72(24): 248705. doi: 10.7498/aps.72.20231060
[5]	管星悦, 黄恒焱, 彭华祺, 刘彦航, 李文飞, 王炜. 生物分子模拟中的机器学习方法. 物理学报, 2023, 72(24): 248708. doi: 10.7498/aps.72.20231624
[6]	邱梓恒, AhmedYousif Ghazal, 龙金友, 张嵩. 三乙胺分子构象与红外光谱的理论研究. 物理学报, 2022, 71(10): 103601. doi: 10.7498/aps.71.20220123
[7]	陈晶晶, 邱小林, 李柯, 周丹, 袁军军. 纳米晶CoNiCrFeMn高熵合金力学性能的原子尺度分析. 物理学报, 2022, 71(19): 199601. doi: 10.7498/aps.71.20220733
[8]	汪杨, 赵伶玲. 单原子Lennard-Jones体黏弹性弛豫时间. 物理学报, 2020, 69(12): 123101. doi: 10.7498/aps.69.20200138
[9]	梁燚然, 梁清. 带电纳米颗粒与相分离的带电生物膜之间相互作用的分子模拟. 物理学报, 2019, 68(2): 028701. doi: 10.7498/aps.68.20181891
[10]	秦亚强, 陈瑞云, 石莹, 周海涛, 张国峰, 秦成兵, 高岩, 肖连团, 贾锁堂. 共轭聚合物单分子构象和能量转移特性研究. 物理学报, 2017, 66(24): 248201. doi: 10.7498/aps.66.248201
[11]	李文飞, 张建, 王骏, 王炜. 生物大分子多尺度理论和计算方法. 物理学报, 2015, 64(9): 098701. doi: 10.7498/aps.64.098701
[12]	周广刚, 卢贵武, 矫玉秋, 李英峰, 王坤, 于养信. KDP晶体固-液界面吸附行为的分子模拟研究. 物理学报, 2012, 61(1): 010204. doi: 10.7498/aps.61.010204
[13]	文德智, 卓仁鸿, 丁大杰, 郑慧, 成晶, 李正宏. 蒙特卡罗模拟中相关变量随机数序列的产生方法. 物理学报, 2012, 61(22): 220204. doi: 10.7498/aps.61.220204
[14]	王克栋, 关君, 朱川川, 刘玉芳. 从头计算研究CH3C(O)OSSOC(O)CH3的构型和能量. 物理学报, 2011, 60(7): 073102. doi: 10.7498/aps.60.073102
[15]	向辉, 刘大欢, 阳庆元, 密建国, 仲崇立. 骨架柔性对短链烷烃分子在金属-有机骨架材料中扩散的影响. 物理学报, 2011, 60(9): 093602. doi: 10.7498/aps.60.093602
[16]	王冬一, 薛春瑜, 仲崇立. 金属-有机骨架材料二聚铜-苯-1，3，5-三羧酸酯中烷烃扩散机理的分子模拟研究. 物理学报, 2009, 58(8): 5552-5559. doi: 10.7498/aps.58.5552
[17]	徐慧, 郭爱敏, 马松山. 碱基序列对DNA分子电子结构的影响. 物理学报, 2007, 56(2): 1208-1213. doi: 10.7498/aps.56.1208
[18]	李凯, 刘红, 张青川, 侯毅, 张广照, 伍小平. 利用微悬臂梁表面应力研究聚N-异丙基丙烯酰胺分子的构象转变. 物理学报, 2006, 55(8): 4111-4116. doi: 10.7498/aps.55.4111
[19]	徐敬. 用分子模拟方法研究羟基乙叉二膦酸(HEDP)在方解石表面的吸附行为. 物理学报, 2006, 55(3): 1107-1112. doi: 10.7498/aps.55.1107
[20]	王光瑞. 带强迫振动项的三分子模型的倍周期分叉序列. 物理学报, 1983, 32(7): 960-972. doi: 10.7498/aps.32.960

计量

文章访问数: 7156
PDF下载量: 177
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

搜索

留言板