Identification of key residues in protein functional movements by using molecular dynamics simulations combined with a perturbation-response scanning method

doi:10.1088/1674-1056/abf12f

Abstract The realization of protein functional movement is usually accompanied by specific conformational changes, and there exist some key residues that mediate and control the functional motions of proteins in the allosteric process. In the present work, the perturbation-response scanning method developed by our group was combined with the molecular dynamics (MD) simulation to identify the key residues controlling the functional movement of proteins. In our method, a physical quantity that is directly related to protein specific function was introduced, and then based on the MD simulation trajectories, the perturbation-response scanning method was used to identify the key residues for functional motions, in which the residues that highly correlated with the fluctuation of the function-related quantity were identified as the key residues controlling the specific functional motions of the protein. Two protein systems, i.e., the heat shock protein 70 and glutamine binding protein, were selected as case studies to validate the effectiveness of our method. Our calculated results are in good agreement with the experimental results. The location of the key residues in the two proteins are similar, indicating the similar mechanisms behind the performance of their biological functions.

Keywords: protein functional movements molecular dynamics simulations perturbation-response scanning method

Received: 06 January 2021
Revised: 25 February 2021
Accepted manuscript online: 24 March 2021

PACS:	87.15.ad	(Analytical theories)
	87.14.E-	(Proteins)
	87.15.hp	(Conformational changes)

Corresponding Authors: Ji-Guo Su
E-mail: jiguosu@ysu.edu.cn

Cite this article:

Jun-Bao Ma(马君宝), Wei-Bu Wang(王韦卜), and Ji-Guo Su(苏计国) Identification of key residues in protein functional movements by using molecular dynamics simulations combined with a perturbation-response scanning method 2021 Chin. Phys. B 30 108701

[1] Su J G, Xu X J, Li C H, Chen W Z and Wang C X 2011 J. Chem. Phys. 135 174101
[2] Monod J, Changeux J P and Jacob F 1963 J. Mol. Biol. 6 306
[3] Perkins J R, Diboun I, Dessailly B H and Lees J G and Orengo C 2010 Structure. 18 1233
[4] Tsai C J, Del Sol A and Nussinov R 2009 Mol. Biosyst. 5 207
[5] Wei X and Wang Y 2021 Chin. Phys. B 30 028703
[6] Teilum K, Olsen J G and Kragelund B B 2009 Cell. Mol. Life Sci. 66 2231
[7] Doshi U, Holliday M J, Eisenmesser E Z and Hamelberg D 2016 Proc. Natl. Acad. Sci. USA 113 4735
[8] Zhou H, Dong Z and Tao P 2018 J. Comput. Chem. 39 1481
[9] Ota N and Agard D A 2005 J. Mol. Biol. 351 345
[10] Sharp K and Skinner J J 2006 Proteins 65 347
[11] Kong Y and Karplus M 2009 Proteins 74 145
[12] Fornili A, Giabbai B, Garau G and Degano M 2010 J. Am. Chem. Soc. 132 17570
[13] Chan C, Wen H, Lu L and Fan J 2015 Chin. Phys. B 25 018707
[14] Shao D and Gao K 2018 Chin. Phys. B 27 018701
[15] Zhang C and Zhou X 2020 Chin. Phys. B 29 108706
[16] Zhang X, Guo Z, Yu P, Li Q, Zhou X and Chen H 2020 Chin. Phys. B 29 078701
[17] McCammon J A 1984 Rep. Prog. Phys. 47 1
[18] Kamberaj H and Van der Vaart A 2009 Biophys. J. 96 1307
[19] Kasahara K, Fukuda I and Nakamura H 2014 PLoS One. 9 e112419
[20] Erman B 2013 Proteins 81 1097
[21] Yang L W, Liu X, Jursa C J, Holliman M, Rader A J, Karimi H A and Bahar I 2005 Bioinformatics 21 2978
[22] Rueda M, Bottegoni G and Abagyan R 2009 J. Chem Inf. Model. 49 716
[23] Tama F, Miyashita O and Brooks Ⅲ C L 2004 J. Mol. Biol. 337 985
[24] Bernardi R C, Melo M C R and Schulten K 2015 Biochim Biophys Acta Gen Subj. 1850 872
[25] Atilgan C, Gerek Z N, Ozkan S B and Atilgan A R 2010 Biophys. J. 99 933
[26] Zheng W, Brooks B R, Doniach S and Thirumalai D 2005 Structure 13 565
[27] Zheng W, Liao J C, Brooks B R and Doniach S 2007 Proteins 67 886
[28] Zheng W and Tekpinar M 2009 BMC Struct. Biol. 9 45
[29] Ming D and Wall M E 2005 Phys. Rev. Lett. 95 198103
[30] Ming D and Wall M E 2005 Proteins 59 697
[31] Su J G, Du H J, Hao R, Xu X J, Li C H, Chen W Z and Wang C X 2013 J. Phys. Chem. B. 117 8689
[32] Su J G, Zhang X, Zhao S X, Li X Y, Hou Y X, Wu Y D, Zhu J Z and An H L 2015 Int. J. Mol. Sci. 16 17933
[33] Su J G, Han X M, Zhang X, Hou Y X, Zhu J Z and Wu Y D 2016 J. Biomol. Struct. Dyn. 34 560
[34] Zhang P F and Su J G 2019 J. Chem. Phys. 151 045101
[35] Tirion M M 1996 Phys. Rev. Lett. 77 1905
[36] Bahar I, Atilgan A R, Demirel M C and Erman B 1998 Phys. Rev. Lett. 80 2733
[37] Lezon T R and Bahar I 2010 PLoS Comput Biol 6 e1000816
[38] Tang Q Y, Zhang Y Y, Wang J, Wang W and Chialvo D R 2017 Phys. Rev. Lett. 118 088102
[39] Bettati S and Mozzarelli A 1997 J. Biol. Chem. 272 32050
[40] Mayer M P and Bukau B 2005 Cell. Mol. Life Sci. 62 670
[41] Rosenzweig R, Nillegoda N B, Mayer M P and Bukau B 2019 Nat. Rev. Mol. Cell Biol. 20 665
[42] Boorstein W R, Ziegelhoffer T and Craig E A 1994 eJ. Mol. Evol. 38 1
[43] Bukau B and Horwich A L 1998 Cell. 92 351
[44] Bhattacharya A, Kurochkin A V, Yip G N, Zhang Y, Bertelsen E B and Zuiderweg E R 2009 J. Mol. Biol. 388 475
[45] Kampinga H H and Craig E A 2010 Nat. Rev. Mol. Cell Biol. 11 579
[46] Woo H J, Jiang J, Lafer E M and Sousa R 2009 Biochemistry. 48 11470
[47] Ung P M U, Thompson A D, Chang L, Gestwicki J E and Carlson H A 2013 PLoS Comput. Biol. 9 e1003279
[48] Mayer M P and Bukau B 2005 Cell. Mol. Life Sci. 62 670
[49] Stetz G and Verkhivker G M 2017 PLoS Comput. Biol. 13 e1005299
[50] Kumar D P, Vorvis C, Sarbeng E B, Ledesma V C C, Willis J E and Liu Q 2011 J. Mol. Biol. 411 1099
[51] Feng Y, Zhang L, Wu S, Liu Z, Gao X, Zhang X, Liu M, Liu J, Huang X and Wang, W 2016 Angew. Chem. Int. Edit. 55 13990
[52] Su J G, Jiao X, Sun T G, Li C H, Chen W Z and Wang C X 2007 Biophys. J. 92 1326
[53] Pang A, Arinaminpathy Y, Sansom M S and Biggin P C 2003 FEBS Lett. 550 168
[54] Sun Y J, Rose J, Wang B C and Hsiao C D 1998 J. Mol. Biol. 278 219
[55] Loeffler H H and Kitao A 2009 Biophys. J. 97 2541
[56] Hayward S and Kitao A 2015 J. Chem. Theory Comput. 11 3895
[57] Lv D, Wang C, Li C, Tan J and Zhang X 2017 Comput. Biol. Chem. 67 62

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Identification of key residues in protein functional movements by using molecular dynamics simulations combined with a perturbation-response scanning method

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