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Protein & Peptide Letters

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ISSN (Online): 1875-5305

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Research Article

Mutational Analysis of Interleukin-11 and its Consequences on Cancer and COVID-19 Related Cytokine Storm -An Extensive Molecular Dynamics Study

Author(s): Sujay Ray* and Shreya Luharuka

Volume 29, Issue 6, 2022

Published on: 05 July, 2022

Page: [514 - 537] Pages: 24

DOI: 10.2174/0929866529666220405102230

Price: $65

Abstract

Background: Interleukin-11 is a pleiotropic cytokine that is known to play an important role in the progression of various forms of cancer by modulating the survival and proliferation of tumour cells. IL11 also demonstrates a structural homology to IL6, the predominant cytokine involved in COVID-19. This makes IL11 a potential therapeutic target in both diseases.

Objective: This study aimed to evaluate the impact of the two-point mutations, R135E and R190E, on the stability of IL11 and their effect on the binding affinity of IL11 with its receptor IL11Rα. It is a molecular level analysis based on the existing experimental validation.

Methods: Computer-aided drug designing techniques, such as molecular modelling, molecular docking, and molecular dynamics simulations, were employed to determine the consequential effects of the two-point mutations.

Results: Our analysis revealed that the two mutations led to a decrease in the overall stability of IL11. This was evident by the increased atomic fluctuations in the mutated regions as well as the corresponding elevation in the deviations seen through RMSD and Rg values. It was also accompanied by a loss in the secondary structural organisation in the mutated proteins. Moreover, mutation R135E led to an increase in the binding affinity of IL11 with IL11Rα and the formation of a more stable complex in comparison to the wild-type protein with its receptor.

Conclusion: Mutation R190E led to the formation of a less stable complex than the wild-type, which suggests a decrease in the binding affinity between IL11 and IL11Rα.

Keywords: IL11, cytokine, molecular dynamics, IL11 receptor alpha subunit, molecular modelling, docking.

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[1]
Ariyama, Y.; Misawa, S.; Sonoda, Y. Synergistic effects of stem cell factor and interleukin 6 or interleukin 11 on the expansion of murine hematopoietic progenitors in liquid suspension culture. Stem Cells, 1995, 13(4), 404-413.
[http://dx.doi.org/10.1002/stem.5530130411] [PMID: 7549899]
[2]
Yonemura, Y.; Kawakita, M.; Masuda, T.; Fujimoto, K.; Kato, K.; Takatsuki, K. Synergistic effects of interleukin 3 and interleukin 11 on murine megakaryopoiesis in serum-free culture. Exp. Hematol., 1992, 20(8), 1011-1016.
[PMID: 1387091]
[3]
McKinley, D.; Wu, Q.; Yang-Feng, T.; Yang, Y.C. Genomic sequence and chromosomal location of human interleukin-11 gene (IL11). Genomics, 1992, 13(3), 814-819.
[http://dx.doi.org/10.1016/0888-7543(92)90158-O] [PMID: 1386338]
[4]
Paul, S.R.; Bennett, F.; Calvetti, J.A.; Kelleher, K.; Wood, C.R.; O’Hara, R.M., Jr; Leary, A.C.; Sibley, B.; Clark, S.C.; Williams, D.A.; Yang, Y.C. Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc. Natl. Acad. Sci. USA, 1990, 87(19), 7512-7516.
[http://dx.doi.org/10.1073/pnas.87.19.7512] [PMID: 2145578]
[5]
Ploemacher, R.E.; van Soest, P.L.; Boudewijn, A. Autocrine transforming growth factor beta 1 blocks colony formation and progenitor cell generation by hemopoietic stem cells stimulated with steel factor. Stem Cells, 1993, 11(4), 336-347.
[http://dx.doi.org/10.1002/stem.5530110412] [PMID: 7691312]
[6]
Dams-Kozlowska, H.; Kwiatkowska-Borowczyk, E.; Gryska, K.; Mackiewicz, A. Designer cytokine hyper interleukin 11 (H11) is a megakaryopoietic factor. Int. J. Med. Sci., 2013, 10(9), 1157-1165.
[http://dx.doi.org/10.7150/ijms.5638] [PMID: 23869192]
[7]
Simpson, R.J.; Hammacher, A.; Smith, D.K.; Matthews, J.M.; Ward, L.D. Interleukin-6: Structure-function relationships. Protein Sci., 1997, 6(5), 929-955.
[http://dx.doi.org/10.1002/pro.5560060501] [PMID: 9144766]
[8]
Taga, T.; Kishimoto, T. Gp130 and the interleukin-6 family of cytokines. Annu. Rev. Immunol., 1997, 15(1), 797-819.
[http://dx.doi.org/10.1146/annurev.immunol.15.1.797] [PMID: 9143707]
[9]
Heinrich, P.C.; Behrmann, I.; Müller-Newen, G.; Schaper, F.; Graeve, L. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem. J., 1998, 334(Pt 2), 297-314.
[http://dx.doi.org/10.1042/bj3340297] [PMID: 9716487]
[10]
Lupardus, P.J.; Skiniotis, G.; Rice, A.J.; Thomas, C.; Fischer, S.; Walz, T.; Garcia, K.C. Structural snapshots of full-length Jak1, a transmembrane gp130/IL-6/IL-6Rα cytokine receptor complex, and the receptor-Jak1 holocomplex. Structure, 2011, 19(1), 45-55.
[http://dx.doi.org/10.1016/j.str.2010.10.010] [PMID: 21220115]
[11]
Bravo, J.; Heath, J.K. Receptor recognition by gp130 cytokines. EMBO J., 2000, 19(11), 2399-2411.
[http://dx.doi.org/10.1093/emboj/19.11.2399] [PMID: 10835339]
[12]
Yamasaki, K.; Taga, T.; Hirata, Y.; Yawata, H.; Kawanishi, Y.; Seed, B.; Taniguchi, T.; Hirano, T.; Kishimoto, T. Cloning and expression of the human interleukin-6 (BSF-2/IFN β 2) receptor. Science, 1988, 241(4867), 825-828.
[http://dx.doi.org/10.1126/science.3136546] [PMID: 3136546]
[13]
Bazan, J.F. Structural design and molecular evolution of a cytokine receptor superfamily. Proc. Natl. Acad. Sci. USA, 1990, 87(18), 6934-6938.
[http://dx.doi.org/10.1073/pnas.87.18.6934] [PMID: 2169613]
[14]
Pflanz, S.; Hibbert, L.; Mattson, J.; Rosales, R.; Vaisberg, E.; Bazan, J.F.; Phillips, J.H.; McClanahan, T.K.; de Waal Malefyt, R.; Kastelein, R.A. WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27. J. Immunol., 2004, 172(4), 2225-2231.
[http://dx.doi.org/10.4049/jimmunol.172.4.2225] [PMID: 14764690]
[15]
Chérel, M.; Sorel, M.; Lebeau, B.; Dubois, S.; Moreau, J.F.; Bataille, R.; Minvielle, S.; Jacques, Y. Molecular cloning of two isoforms of a receptor for the human hematopoietic cytokine interleukin-11. Blood, 1995, 86(7), 2534-2540.
[http://dx.doi.org/10.1182/blood.V86.7.2534.bloodjournal8672534] [PMID: 7670098]
[16]
Schleinkofer, K.; Dingley, A.; Tacken, I.; Federwisch, M.; Müller-Newen, G.; Heinrich, P.C.; Vusio, P.; Jacques, Y.; Grötzinger, J. Identification of the domain in the human interleukin-11 receptor that mediates ligand binding. J. Mol. Biol., 2001, 306(2), 263-274.
[http://dx.doi.org/10.1006/jmbi.2000.4387] [PMID: 11237599]
[17]
Xu, D.H.; Zhu, Z.; Wakefield, M.R.; Xiao, H.; Bai, Q.; Fang, Y. The role of IL-11 in immunity and cancer. Cancer Lett., 2016, 373(2), 156-163.
[http://dx.doi.org/10.1016/j.canlet.2016.01.004] [PMID: 26826523]
[18]
Tacken, I.; Dahmen, H.; Boisteau, O.; Minvielle, S.; Jacques, Y.; Grötzinger, J.; Küster, A.; Horsten, U.; Blanc, C.; Montero-Julian, F.A.; Heinrich, P.C.; Müller-Newen, G. Definition of receptor binding sites on human interleukin-11 by molecular modeling-guided mutagenesis. Eur. J. Biochem., 1999, 265(2), 645-655.
[http://dx.doi.org/10.1046/j.1432-1327.1999.00755.x] [PMID: 10504396]
[19]
Garbers, C.; Scheller, J. Interleukin-6 and interleukin-11: Same same but different. Biol. Chem., 2013, 394(9), 1145-1161.
[http://dx.doi.org/10.1515/hsz-2013-0166] [PMID: 23740659]
[20]
Metcalfe, R.D.; Putoczki, T.L.; Griffin, M.D.W. Structural understanding of interleukin 6 family cytokine signaling and targeted therapies: Focus on interleukin 11. Front. Immunol., 2020, 11, 1424.
[http://dx.doi.org/10.3389/fimmu.2020.01424] [PMID: 32765502]
[21]
McGonagle, D.; Sharif, K.; O’Regan, A.; Bridgewood, C. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun. Rev., 2020, 19(6), 102537.
[http://dx.doi.org/10.1016/j.autrev.2020.102537] [PMID: 32251717]
[22]
Chen, L.; Liu, H.G.; Liu, W.; Liu, J.; Liu, K.; Shang, J.; Deng, Y.; Wei, S. Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi, Chinese J. Tuberc Respir. Dis., 2020, 43(0), E005.
[http://dx.doi.org/10.3760/cma.j.issn.1001-0939.2020.0005] [PMID: 32026671]
[23]
Coperchini, F.; Chiovato, L.; Croce, L.; Magri, F.; Rotondi, M. The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev., 2020, 53, 25-32.
[http://dx.doi.org/10.1016/j.cytogfr.2020.05.003] [PMID: 32446778]
[24]
Ragab, D.; Salah Eldin, H.; Taeimah, M.; Khattab, R.; Salem, R. The COVID-19 cytokine storm; What we know so far. Front. Immunol., 2020, 11, 1446.
[http://dx.doi.org/10.3389/fimmu.2020.01446] [PMID: 32612617]
[25]
Ruan, Q.; Yang, K.; Wang, W.; Jiang, L.; Song, J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med., 2020, 46(5), 846-848.
[http://dx.doi.org/10.1007/s00134-020-05991-x] [PMID: 32125452]
[26]
Ng, B.; Cook, S.A.; Schafer, S. Interleukin-11 signaling underlies fibrosis, parenchymal dysfunction, and chronic inflammation of the airway. Exp. Mol. Med., 2020, 52(12), 1871-1878.
[http://dx.doi.org/10.1038/s12276-020-00531-5] [PMID: 33262481]
[27]
Trepicchio, W.L.; Bozza, M.; Pedneault, G.; Dorner, A.J. Recombinant human IL-11 attenuates the inflammatory response through down-regulation of proinflammatory cytokine release and nitric oxide production. J. Immunol., 1996, 157(8), 3627-3634.
[PMID: 8871663]
[28]
Redlich, C.A.; Gao, X.; Rockwell, S.; Kelley, M.; Elias, J.A. IL-11 enhances survival and decreases TNF production after radiation-induced thoracic injury. J. Immunol., 1996, 157(4), 1705-1710.
[PMID: 8759759]
[29]
Hanavadi, S.; Martin, T.A.; Watkins, G.; Mansel, R.E.; Jiang, W.G. Expression of interleukin 11 and its receptor and their prognostic value in human breast cancer. Ann. Surg. Oncol., 2006, 13(6), 802-808.
[http://dx.doi.org/10.1245/ASO.2006.05.028] [PMID: 16614887]
[30]
Lay, V.; Yap, J.; Sonderegger, S.; Dimitriadis, E. Interleukin 11 regulates endometrial cancer cell adhesion and migration via STAT3. Int. J. Oncol., 2012, 41(2), 759-764.
[http://dx.doi.org/10.3892/ijo.2012.1486] [PMID: 22614117]
[31]
Campbell, C.L.; Jiang, Z.; Savarese, D.M.F.; Savarese, T.M. Increased expression of the interleukin-11 receptor and evidence of STAT3 activation in prostate carcinoma. Am. J. Pathol., 2001, 158(1), 25-32.
[http://dx.doi.org/10.1016/S0002-9440(10)63940-5] [PMID: 11141475]
[32]
Campbell, C.L.; Guardiani, R.; Ollari, C.; Nelson, B.E.; Quesenberry, P.J.; Savarese, T.M. Interleukin-11 receptor expression in primary ovarian carcinomas. Gynecol. Oncol., 2001, 80(2), 121-127.
[http://dx.doi.org/10.1006/gyno.2000.6064] [PMID: 11161848]
[33]
Howlett, M.; Giraud, A.S.; Lescesen, H.; Jackson, C.B.; Kalantzis, A.; Van Driel, I.R.; Robb, L.; Van der Hoek, M.; Ernst, M.; Minamoto, T.; Boussioutas, A.; Oshima, H.; Oshima, M.; Judd, L.M. The interleukin-6 family cytokine interleukin-11 regulates homeostatic epithelial cell turnover and promotes gastric tumor development. Gastroenterology, 2009, 136(3), 967-977.
[http://dx.doi.org/10.1053/j.gastro.2008.12.003] [PMID: 19121317]
[34]
Putoczki, T.; Ernst, M. More than a sidekick: The IL-6 family cytokine IL-11 links inflammation to cancer. J. Leukoc. Biol., 2010, 88(6), 1109-1117.
[http://dx.doi.org/10.1189/jlb.0410226] [PMID: 20610798]
[35]
Yamazumi, K.; Nakayama, T.; Kusaba, T.; Wen, C.Y.; Yoshizaki, A.; Yakata, Y.; Nagayasu, T.; Sekine, I. Expression of interleukin-11 and interleukin-11 receptor α in human colorectal adenocarcinoma; immunohistochemical analyses and correlation with clinicopathological factors. World J. Gastroenterol., 2006, 12(2), 317-321.
[http://dx.doi.org/10.3748/wjg.v12.i2.317] [PMID: 16482637]
[36]
Johnstone, C.N.; Chand, A.; Putoczki, T.L.; Ernst, M. Emerging roles for IL-11 signaling in cancer development and progression: Focus on breast cancer. Cytokine Growth Factor Rev., 2015, 26(5), 489-498.
[http://dx.doi.org/10.1016/j.cytogfr.2015.07.015] [PMID: 26209885]
[37]
Heinrich, P.C.; Behrmann, I.; Haan, S.; Hermanns, H.M.; Müller-Newen, G.; Schaper, F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem. J., 2003, 374(Pt 1), 1-20.
[http://dx.doi.org/10.1042/bj20030407] [PMID: 12773095]
[38]
Bateman, A. UniProt Consortium. UniProt: A worldwide hub of protein knowledge. Nucleic Acids Res., 2019, 47(D1), D506-D515.
[http://dx.doi.org/10.1093/nar/gky1049] [PMID: 30395287]
[39]
Martin, A.C.R.; Orengo, C.A.; Hutchinson, E.G.; Jones, S.; Karmirantzou, M.; Laskowski, R.A.; Mitchell, J.B.O.; Taroni, C.; Thornton, J.M. Protein folds and functions. Structure, 1998, 6(7), 875-884.
[http://dx.doi.org/10.1016/S0969-2126(98)00089-6] [PMID: 9687369]
[40]
Mistry, J.; Chuguransky, S.; Williams, L.; Qureshi, M.; Salazar, G.A.; Sonnhammer, E.L.L.; Tosatto, S.C.E.; Paladin, L.; Raj, S.; Richardson, L.J.; Finn, R.D.; Bateman, A. Pfam: The protein families database in 2021. Nucleic Acids Res., 2021, 49(D1), D412-D419.
[http://dx.doi.org/10.1093/nar/gkaa913] [PMID: 33125078]
[41]
Ponting, C.P.; Schultz, J.; Milpetz, F.; Bork, P. SMART: Identification and annotation of domains from signalling and extracellular protein sequences. Nucleic Acids Res., 1999, 27(1), 229-232.
[http://dx.doi.org/10.1093/nar/27.1.229] [PMID: 9847187]
[42]
Sigrist, C.J.A.; de Castro, E.; Cerutti, L.; Cuche, B.A.; Hulo, N.; Bridge, A.; Bougueleret, L.; Xenarios, I. New and continuing developments at PROSITE. Nucleic Acids Res., 2013, 41(Database issue), D344-D347.
[PMID: 23161676]
[43]
Lu, S.; Wang, J.; Chitsaz, F.; Derbyshire, M.K.; Geer, R.C.; Gonzales, N.R.; Gwadz, M.; Hurwitz, D.I.; Marchler, G.H.; Song, J.S.; Thanki, N.; Yamashita, R.A.; Yang, M.; Zhang, D.; Zheng, C.; Lanczycki, C.J.; Marchler-Bauer, A. CDD/SPARCLE: The conserved domain database in 2020. Nucleic Acids Res., 2020, 48(D1), D265-D268.
[http://dx.doi.org/10.1093/nar/gkz991] [PMID: 31777944]
[44]
Waterhouse, A.; Bertoni, M.; Bienert, S.; Studer, G.; Tauriello, G.; Gumienny, R.; Heer, F.T.; de Beer, T.A.P.; Rempfer, C.; Bordoli, L.; Lepore, R.; Schwede, T. SWISS-MODEL: Homology modelling of protein structures and complexes. Nucleic Acids Res., 2018, 46(W1), W296-W303.
[http://dx.doi.org/10.1093/nar/gky427] [PMID: 29788355]
[45]
Webb, B.; Sali, A. Comparative protein structure modeling using modeller. Curr. Protoc. Bioinform., 2016, 2016, 5.6.1-5.6.37.
[46]
Källberg, M.; Wang, H.; Wang, S.; Peng, J.; Wang, Z.; Lu, H.; Xu, J. Template-based protein structure modeling using the RaptorX web server. Nat. Protoc., 2012, 7(8), 1511-1522.
[http://dx.doi.org/10.1038/nprot.2012.085] [PMID: 22814390]
[47]
Kelley, L.A.; Mezulis, S.; Yates, C.M.; Wass, M.N.; Sternberg, M.J. Trabajo práctico No 13. varianzas en función de variable independiente categórica. Nat. Protoc., 2016, 10(6), 845-858.
[http://dx.doi.org/10.1038/nprot.2015.053] [PMID: 25950237]
[48]
Kim, D.E.; Chivian, D.; Baker, D. Protein structure prediction and analysis using the robetta server. Nucleic Acids Res., 2004, 32, 526-526.
[http://dx.doi.org/10.1093/nar/gkh468]
[49]
Metcalfe, R.D.; Aizel, K.; Zlatic, C.O.; Nguyen, P.M.; Morton, C.J.; Lio, D.S.S.; Cheng, H.C.; Dobson, R.C.J.; Parker, M.W.; Gooley, P.R.; Putoczki, T.L.; Griffin, M.D.W. The structure of the extracellular domains of human interleukin 11α receptor reveals mechanisms of cytokine engagement. J. Biol. Chem., 2020, 295(24), 8285-8301.
[http://dx.doi.org/10.1074/jbc.RA119.012351] [PMID: 32332100]
[50]
Madeira, F.; Park, Y.M.; Lee, J.; Buso, N.; Gur, T.; Madhusoodanan, N.; Basutkar, P.; Tivey, A.R.N.; Potter, S.C.; Finn, R.D.; Lopez, R. The EMBL-EBI search and sequence analysis tools APIs in 2019. Nucleic Acids Res., 2019, 47(W1), W636-W641.
[http://dx.doi.org/10.1093/nar/gkz268] [PMID: 30976793]
[51]
Colovos, C.; Yeates, T.O. Verification of protein structures: Patterns of nonbonded atomic interactions. Protein Sci., 1993, 2(9), 1511-1519.
[http://dx.doi.org/10.1002/pro.5560020916] [PMID: 8401235]
[52]
Lüthy, R.; Bowie, J.U.; Eisenberg, D. Assessment of protein models with three-dimensional profiles. Nature, 1992, 356(6364), 83-85.
[http://dx.doi.org/10.1038/356083a0] [PMID: 1538787]
[53]
Laskowski, R.A.; MacArthur, M.W.; Moss, D.S.; Thornton, J.M. PROCHECK: A program to check the stereochemical quality of protein structures. J. Appl. Cryst., 1993, 26(2), 283-291.
[http://dx.doi.org/10.1107/S0021889892009944]
[54]
Wiederstein, M.; Sippl, M.J. ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res., 2007, 35(Suppl. 2), W407-10.
[http://dx.doi.org/10.1093/nar/gkm290] [PMID: 17517781]
[55]
Xu, D.; Zhang, Y. Improving the physical realism and structural accuracy of protein models by a two-step atomic-level energy minimization. Biophys. J., 2011, 101(10), 2525-2534.
[56]
Fiser, A.; Sali, A. ModLoop: Automated modeling of loops in protein structures. Bioinformatics, 2003, 19(18), 2500-2501.
[http://dx.doi.org/10.1093/bioinformatics/btg362] [PMID: 14668246]
[57]
Frishman, D.; Argos, P. Knowledge-based protein secondary structure assignment. Proteins, 1995, 23(4), 566-579.
[http://dx.doi.org/10.1002/prot.340230412] [PMID: 8749853]
[58]
Heinig, M.; Frishman, D. STRIDE: A web server for secondary structure assignment from known atomic coordinates of proteins. Nucleic Acids Res., 2004, 32, W500-W502.
[http://dx.doi.org/10.1093/nar/gkh429]
[59]
Lindahl; Abraham; Hess; Spoel, van der. GROMACS 2020.1 Manual. 2020.
[60]
MacKerell, A.D. Jr.; Banavali, N.; Foloppe, N. Development and current status of the CHARMM force field for nucleic acids. Biopolymers, 2001, 56(4), 257-265.
[http://dx.doi.org/10.1002/1097-0282(2000)56:4<257::AID-BIP10029>3.0.CO;2-W] [PMID: 11754339]
[61]
Van Der Spoel, D.; Lindahl, E.; Hess, B.; Groenhof, G.; Mark, A.E.; Berendsen, H.J.C. GROMACS: Fast, flexible, and free. J. Comput. Chem., 2005, 26(16), 1701-1718.
[http://dx.doi.org/10.1002/jcc.20291] [PMID: 16211538]
[62]
Van Gunsteren, W.F.; Berendsen, H.J.C. Computer simulation of molecular dynamics: Methodology, applications, and perspectives in chemistry. Angew. Chem. Int. Ed. Engl., 1990, 29(9), 992-1023.
[http://dx.doi.org/10.1002/anie.199009921]
[63]
Mark, P.; Nilsson, L. Structure and dynamics of the TIP3P, SPC, and SPC/E water models at 298 K. J. Phys. Chem. A, 2001, 105(43), 9954-9960.
[http://dx.doi.org/10.1021/jp003020w]
[64]
Humphrey, W.; Dalke, A.; Schulten, K. VMD: Visual molecular dynamics. J. Mol. Graph., 1996, 14(1), 33-38, 27-28.
[http://dx.doi.org/10.1016/0263-7855(96)00018-5] [PMID: 8744570]
[65]
van Zundert, G.C.P.; Rodrigues, J.P.G.L.M.; Trellet, M.; Schmitz, C.; Kastritis, P.L.; Karaca, E.; Melquiond, A.S.J.; van Dijk, M.; de Vries, S.J.; Bonvin, A.M.J.J. The HADDOCK2.2 web server: User-friendly integrative modeling of biomolecular complexes. J. Mol. Biol., 2016, 428(4), 720-725.
[http://dx.doi.org/10.1016/j.jmb.2015.09.014] [PMID: 26410586]
[66]
Laskowski, R.A.; Swindells, M.B. LigPlot+: Multiple ligand-protein interaction diagrams for drug discovery. J. Chem. Inf. Model., 2011, 51(10), 2778-2786.
[http://dx.doi.org/10.1021/ci200227u] [PMID: 21919503]
[67]
Tina, K.G.; Bhadra, R.; Srinivasan, N. PIC: Protein interactions calculator. Nucleic Acids Res., 2007, 35, W473-W476.
[PMID: 17584791]
[68]
Bahar, I.; Atilgan, A.R.; Demirel, M.C.; Erman, B. Vibrational dynamics of folded proteins: Significance of slow and fast motions in relation to function and stability. Phys. Rev. Lett., 1998, 80(12), 2733-2736.
[http://dx.doi.org/10.1103/PhysRevLett.80.2733]
[69]
Biswas, R.; Chowdhury, N.; Biswas, S.; Roy, R.; Bagchi, A. Structure based virtual screening of natural products to disrupt the structural integrity of TRAF6 C-terminal domain homotrimer. J. Mol. Graph. Model., 2019, 93, 107428.
[http://dx.doi.org/10.1016/j.jmgm.2019.08.005] [PMID: 31493661]
[70]
Kukol, A. Molecular Modeling of Proteins; Springer: Berlin, Heidelberg Humana New York, , 2014; p. 1215.
[71]
Ippoliti, E. Analysis of MD Simulations; University Of Illinois at Urbana-Champaign: IL, USA, , 2010; pp. 1-42.
[72]
Richards, F.M.; Kundrot, C.E. Identification of structural motifs from protein coordinate data: Secondary structure and first-level supersecondary structure. Proteins, 1988, 3(2), 71-84.
[http://dx.doi.org/10.1002/prot.340030202] [PMID: 3399495]
[73]
Pikkemaat, M.G.; Linssen, A.B.M.; Berendsen, H.J.C.; Janssen, D.B. Molecular dynamics simulations as a tool for improving protein stability. Protein Eng., 2002, 15(3), 185-192.
[http://dx.doi.org/10.1093/protein/15.3.185] [PMID: 11932489]
[74]
Bornot, A.; Etchebest, C.; de Brevern, A.G. Predicting protein flexibility through the prediction of local structures. Proteins, 2011, 79(3), 839-852.
[http://dx.doi.org/10.1002/prot.22922] [PMID: 21287616]
[75]
Lobanov, M.Y.; Bogatyreva, N.S.; Galzitskaya, O.V. Radius of gyration as an indicator of protein structure compactness. Mol. Biol., 2008, 42(4), 623-628.
[http://dx.doi.org/10.1134/S0026893308040195] [PMID: 18856071]
[76]
Sklenar, H.; Etchebest, C.; Lavery, R. Describing protein structure: A general algorithm yielding complete helicoidal parameters and a unique overall axis. Proteins, 1989, 6(1), 46-60.
[http://dx.doi.org/10.1002/prot.340060105] [PMID: 2608659]
[77]
Bagchi, A.; Ghosh, T.C. Structural interaction between DsrE-DsrF-DsrH proteins involved in the transport of electrons in the Dsr operon. J. Biomol. Struct. Dyn., 2008, 25(5), 517-523.
[http://dx.doi.org/10.1080/07391102.2008.10507198] [PMID: 18282006]
[78]
David, C.C.; Jacobs, D.J. Principal component analysis: A method for determining the essential dynamics of proteins. Methods Mol. Biol., 2014, 1084, 193-226.
[http://dx.doi.org/10.1007/978-1-62703-658-0_11] [PMID: 24061923]
[79]
Londhe, A.M.H.; Gadhe, C.G.; Lim, S.M.; Pae, A.N. Investigation of molecular details of Keap1-Nrf2 inhibitors using molecular dynamics and umbrella sampling techniques. Molecules, 2019, 24(22), 4085.
[http://dx.doi.org/10.3390/molecules24224085] [PMID: 31726716]
[80]
Meyer, E.E.; Rosenberg, K.J.; Israelachvili, J. Recent progress in understanding hydrophobic interactions. Proc. Natl. Acad. Sci. USA, 2006, 103(43), 15739-15746.
[http://dx.doi.org/10.1073/pnas.0606422103] [PMID: 17023540]
[81]
Wilkinson, A.J.; Fersht, A.R.; Blow, D.M.; Carter, P.; Winter, G. A large increase in enzyme-substrate affinity by protein engineering. Nature, 1984, 307(5947), 187-188.
[http://dx.doi.org/10.1038/307187a0] [PMID: 6690998]
[82]
Kuhn, B.; Mohr, P.; Stahl, M. Intramolecular hydrogen bonding in medicinal chemistry. J. Med. Chem., 2010, 53(6), 2601-2611.
[http://dx.doi.org/10.1021/jm100087s] [PMID: 20175530]

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