Molecular dynamics simulations provide structural insight into binding of cyclic dinucleotides to human STING protein

References

• Allen, W. J., Balius, T. E., Mukherjee, S., Brozell, S. R., Moustakas, D. T., Lang, P. T., Case, D. A., Kuntz, I. D., & Rizzo, R. C. (2015). DOCK 6: Impact of new features and current docking performance. Journal of Computational Chemistry, 36(15), 1132–1156. https://doi.org/10.1002/jcc.23905
   PubMed Web of Science ®Google Scholar
• Amitai, G., Shemesh, A., Sitbon, E., Shklar, M., Netanely, D., Venger, I., & Pietrokovski, S. (2004). Network analysis of protein structures identifies functional residues. Journal of Molecular Biology, 344(4), 1135–1146. https://doi.org/10.1016/j.jmb.2004.10.055
   PubMed Web of Science ®Google Scholar
• Anwar, M. A., & Choi, S. (2017). Structure-Activity Relationship in TLR4 Mutations: Atomistic molecular dynamics simulations and residue interaction network analysis. Scientific Reports, 7, 43807. https://doi.org/10.1038/srep43807
   PubMed Web of Science ®Google Scholar
• Baguley, B. C., & Ching, L. M. (2002). DMXAA: An antivascular agent with multiple host responses. International Journal of Radiation Oncology, Biology, Physics, 54(5), 1503–1511. https://doi.org/10.1016/S0360-3016(02)03920-2
   PubMed Web of Science ®Google Scholar
• Baron, R., Setny, P., & McCammon, J. A. (2010). Water in cavity-ligand recognition. Journal of the American Chemical Society, 132(34), 12091–12097. https://doi.org/10.1021/ja1050082
   PubMed Web of Science ®Google Scholar
• Bayly, C. I., Cieplak, P., Cornell, W. D., & Kollman, P. A. (1993). A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges - the resp model. The Journal of Physical Chemistry, 97(40), 10269–10280. https://doi.org/10.1021/j100142a004
   Web of Science ®Google Scholar
• Berman, H. M., Battistuz, T., Bhat, T. N., Bluhm, W. F., Bourne, P. E., Burkhardt, K., Feng, Z., Gilliland, G. L., Iype, L., Jain, S., Fagan, P., Marvin, J., Padilla, D., Ravichandran, V., Schneider, B., Thanki, N., Weissig, H., Westbrook, J. D., & Zardecki, C. (2002). The protein data bank. Acta Crystallographica. Section D, Biological Crystallography, 58(Pt 6 No 1), 899–907. https://doi.org/10.1107/s0907444902003451
   PubMedGoogle Scholar
• Bode, C., Kovacs, I. A., Szalay, M. S., Palotai, R., Korcsmaros, T., & Csermely, P. (2007). Network analysis of protein dynamics. FEBS Letters, 581(15), 2776–2782. https://doi.org/10.1016/j.febslet.2007.05.021
   PubMed Web of Science ®Google Scholar
• Bowman, G. R., Bolin, E. R., Hart, K. M., Maguire, B. C., & Marqusee, S. (2015). Discovery of multiple hidden allosteric sites by combining Markov state models and experiments. Proceedings of the National Academy of Sciences of the United States of America, 112(9), 2734–2739. https://doi.org/10.1073/pnas.1417811112
   PubMed Web of Science ®Google Scholar
• Burdette, D. L., & Vance, R. E. (2013). STING and the innate immune response to nucleic acids in the cytosol. Nature Immunology, 14(1), 19–26. https://doi.org/10.1038/ni.2491
   PubMed Web of Science ®Google Scholar
• Burley, S. K., Berman, H. M., Bhikadiya, C., Bi, C., Chen, L., Di Costanzo, L., Christie, C., Dalenberg, K., Duarte, J. M., Dutta, S., Feng, Z., Ghosh, S., Goodsell, D. S., Green, R. K., Guranovic, V., Guzenko, D., Hudson, B. P., Kalro, T., Liang, Y., … Zardecki, C. (2019). RCSB protein data bank: Biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy. Nucleic Acids Research, 47(D1), D464–D474. https://doi.org/10.1093/nar/gky1004
   PubMed Web of Science ®Google Scholar
• Case, D. A., Betz, R. M., Cerutti, D. S., Cheatham, T. E., I.; Darden, T. A., Duke, R. E., Giese, T. J., Gohlke, H., Goetz, A. W., Homeyer, N., Izadi, S., Janowski, P., Kaus, J., Kovalenko, A., Lee, T. S., LeGrand, S., Li, P., Lin, C., Luchko, T., Luo, R., … Kollman, P. A. (2016). AMBER 2016. University of California.
   Google Scholar
• Cavlar, T., Deimling, T., Ablasser, A., Hopfner, K. P., & Hornung, V. (2013). Species-specific detection of the antiviral small-molecule compound CMA by STING. The EMBO Journal, 32(10), 1440–1450. https://doi.org/10.1038/emboj.2013.86
   PubMed Web of Science ®Google Scholar
• Černý, J., Božíková, P., Balík, A., Marques, S. M., & Vyklický, L. (2019). NMDA receptor opening and closing-transitions of a molecular machine revealed by molecular dynamics. Biomolecules, 9(10), 546. https://doi.org/10.3390/biom9100546
   PubMed Web of Science ®Google Scholar
• Chin, E. N., Yu, C., Vartabedian, V. F., Jia, Y., Kumar, M., Gamo, A. M., Vernier, W., Ali, S. H., Kissai, M., Lazar, D. C., Nguyen, N., Pereira, L. E., Benish, B., Woods, A. K., Joseph, S. B., Chu, A., Johnson, K. A., Sander, P. N., Martinez-Pena, F., … Lairson, L. L. (2020). Antitumor activity of a systemic STING-activating non-nucleotide cGAMP mimetic. Science (New York, NY), 369(6506), 993–999. https://doi.org/10.1126/science.abb4255
   Google Scholar
• Corrales, L., Glickman, L. H., McWhirter, S. M., Kanne, D. B., Sivick, K. E., Katibah, G. E., Woo, S. R., Lemmens, E., Banda, T., Leong, J. J., Metchette, K., Dubensky, T. W., Jr., & Gajewski, T. F. (2015). Direct Activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Reports, 11(7), 1018–1030. https://doi.org/10.1016/j.celrep.2015.04.031
   PubMed Web of Science ®Google Scholar
• Cui, X., Zhang, R., Cen, S., & Zhou, J. (2019). STING modulators: Predictive significance in drug discovery. European Journal of Medicinal Chemistry, 182, 111591. https://doi.org/10.1016/j.ejmech.2019.111591
   PubMed Web of Science ®Google Scholar
• Davidson, R. M., Lauritzen, A., & Seneff, S. (2013). Biological water dynamics and entropy: A biophysical origin of cancer and other diseases. Entropy, 15(12), 3822–3876. https://doi.org/10.3390/e15093822
   Google Scholar
• del Sol, A., Fujihashi, H., Amoros, D., & Nussinov, R. (2006). Residues crucial for maintaining short paths in network communication mediate signaling in proteins. Molecular Systems Biology, 2(1), 0019. https://doi.org/10.1038/msb4100063
   PubMedGoogle Scholar
• Diner, E. J., Burdette, D. L., Wilson, S. C., Monroe, K. M., Kellenberger, C. A., Hyodo, M., Hayakawa, Y., Hammond, M. C., & Vance, R. E. (2013). The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING. Cell Reports, 3(5), 1355–1361. https://doi.org/10.1016/j.celrep.2013.05.009
   PubMed Web of Science ®Google Scholar
• Doerr, S., Harvey, M. J., Noe, F., & De Fabritiis, G. (2016). HTMD: High-Throughput molecular dynamics for molecular discovery. Journal of Chemical Theory and Computation, 12(4), 1845–1852. https://doi.org/10.1021/acs.jctc.6b00049
   PubMed Web of Science ®Google Scholar
• Efficacy and Safety Trial of ADU-S100 and Pembrolizumab in Head and Neck Cancer (2019). ClinicalTrials.gov Identifier: NCT03937141. https://clinicaltrials.gov/ct2/show/NCT03937141.
   Google Scholar
• Feng, X., Liu, D., Li, Z., & Bian, J. (2020). Bioactive modulators targeting STING adaptor in cGAS-STING pathway. Drug Discovery Today, 25(1), 230–237. https://doi.org/10.1016/j.drudis.2019.11.007
   PubMed Web of Science ®Google Scholar
• Fletcher, R., & Powell, M. J. D. (1963). A rapidly convergent descent method for minimization. The Computer Journal, 6(2), 163–168. https://doi.org/10.1093/comjnl/6.2.163
   Web of Science ®Google Scholar
• Fletcher, R., & Reeves, C. M. (1964). Function minimization by conjugate gradients. The Computer Journal, 7(2), 149–154. https://doi.org/10.1093/comjnl/7.2.149
   Web of Science ®Google Scholar
• Fuertes, M. B., Woo, S. R., Burnett, B., Fu, Y. X., & Gajewski, T. F. (2013). Type I interferon response and innate immune sensing of cancer. Trends in Immunology, 34(2), 67–73. https://doi.org/10.1016/j.it.2012.10.004
   PubMed Web of Science ®Google Scholar
• Gao, P., Ascano, M., Zillinger, T., Wang, W., Dai, P., Serganov, A. A., Gaffney, B. L., Shuman, S., Jones, R. A., Deng, L., Hartmann, G., Barchet, W., Tuschl, T., & Patel, D. J. (2013). Structure-function analysis of STING activation by c[G(2',5')pA(3',5')p] and targeting by antiviral DMXAA. Cell, 154(4), 748–762. https://doi.org/10.1016/j.cell.2013.07.023
   PubMed Web of Science ®Google Scholar
• Grant, B. J., Rodrigues, A. P., ElSawy, K. M., McCammon, J. A., & Caves, L. S. (2006). Bio3d: An R package for the comparative analysis of protein structures. Bioinformatics, 22(21), 2695–2696. https://doi.org/10.1093/bioinformatics/btl461
   PubMed Web of Science ®Google Scholar
• Gutten, O., Bím, D., Řezáč, J., & Rulíšek, L. (2018). Macrocycle conformational sampling by DFT-D3/COSMO-RS Methodology. Journal of Chemical Information and Modeling, 58(1), 48–60. https://doi.org/10.1021/acs.jcim.7b00453
   PubMed Web of Science ®Google Scholar
• Gutten, O., Jurečka, P., Aliakbar Tehrani, Z., Buděšínský, M., Řezáč, J., & Rulíšek, L. (2021). Conformational energies and equilibria of cyclic dinucleotides in vacuo and in solution: Computational chemistry vs. NMR Experiments. Physical Chemistry Chemical Physics: Pccp, 23(12), 7280–7294. https://doi.org/10.1039/D0CP05993E
   PubMed Web of Science ®Google Scholar
• Haag, S. M., Gulen, M. F., Reymond, L., Gibelin, A., Abrami, L., Decout, A., Heymann, M., van der Goot, F. G., Turcatti, G., Behrendt, R., & Ablasser, A. (2018). Targeting STING with covalent small-molecule inhibitors. Nature, 559(7713), 269–273. https://doi.org/10.1038/s41586-018-0287-8
   PubMed Web of Science ®Google Scholar
• Hu, G., Zhou, J., Yan, W., Chen, J., & Shen, B. (2013). The topology and dynamics of protein complexes: Insights from intra- molecular network theory. Current Protein & Peptide Science, 14(2), 121–132. https://doi.org/10.2174/1389203711314020004
   PubMed Web of Science ®Google Scholar
• Huang, Y. H., Liu, X. Y., Du, X. X., Jiang, Z. F., & Su, X. D. (2012). The structural basis for the sensing and binding of cyclic di-GMP by STING. Nature Structural & Molecular Biology, 19(7), 728–730. https://doi.org/10.1038/nsmb.2333
   PubMed Web of Science ®Google Scholar
• Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD: Visual molecular dynamics. Journal of Molecular Graphics, 14(1), 33–38. https://doi.org/10.1016/0263-7855(96)00018-5
   PubMedGoogle Scholar
• Ishikawa, H., Ma, Z., & Barber, G. N. (2009). STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature, 461(7265), 788–792. https://doi.org/10.1038/nature08476
   PubMed Web of Science ®Google Scholar
• Jiao, X., & Chang, S. (2011). Scoring function based on weighted residue network. International Journal of Molecular Sciences, 12(12), 8773–8786. https://doi.org/10.3390/ijms12128773
   PubMed Web of Science ®Google Scholar
• Karamzadeh, R., Karimi-Jafari, M. H., Sharifi-Zarchi, A., Chitsaz, H., Salekdeh, G. H., & Moosavi-Movahedi, A. A. (2017). Machine learning and network analysis of molecular dynamics trajectories reveal two chains of red/Ox-specific residue interactions in human protein disulfide isomerase. Scientific Reports, 7(1), 3666. https://doi.org/10.1038/s41598-017-03966-5
   PubMedGoogle Scholar
• Keating, S. E., Baran, M., & Bowie, A. G. (2011). Cytosolic DNA sensors regulating type I interferon induction. Trends in Immunology, 32(12), 574–581. https://doi.org/10.1016/j.it.2011.08.004
   PubMed Web of Science ®Google Scholar
• Kumar, V. (2019). A STING to inflammation and autoimmunity. Journal of Leukocyte Biology, 106(1), 171–185. https://doi.org/10.1002/JLB.4MIR1018-397RR
   PubMed Web of Science ®Google Scholar
• Li, S., Hong, Z., Wang, Z., Li, F., Mei, J., Huang, L., Lou, X., Zhao, S., Song, L., Chen, W., Wang, Q., Liu, H., Cai, Y., Yu, H., Xu, H., Zeng, G., Wang, Q., Zhu, J., Liu, X., Tan, N., & Wang, C. (2018). The cyclopeptide astin C specifically inhibits the innate immune CDN sensor STING. Cell Reports, 25(12), 3405–3421 e7. https://doi.org/10.1016/j.celrep.2018.11.097
   PubMed Web of Science ®Google Scholar
• Lioux, T., Mauny, M. A., Lamoureux, A., Bascoul, N., Hays, M., Vernejoul, F., Baudru, A. S., Boularan, C., Lopes-Vicente, J., Qushair, G., & Tiraby, G. (2016). Design, synthesis, and biological evaluation of novel Cyclic Adenosine-Inosine Monophosphate (cAIMP) analogs that activate Stimulator of Interferon Genes (STING). Journal of Medicinal Chemistry, 59(22), 10253–10267. https://doi.org/10.1021/acs.jmedchem.6b01300
   PubMed Web of Science ®Google Scholar
• Maier, J. A., Martinez, C., Kasavajhala, K., Wickstrom, L., Hauser, K. E., & Simmerling, C. (2015). ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99SB. Journal of Chemical Theory and Computation, 11(8), 3696–3713. https://doi.org/10.1021/acs.jctc.5b00255
   PubMed Web of Science ®Google Scholar
• Maurer, M., & Oostenbrink, C. (2019). Water in protein hydration and ligand recognition. Journal of Molecular Recognition : JMR, 32(12), e2810. https://doi.org/10.1002/jmr.2810
   PubMed Web of Science ®Google Scholar
• Mishra, S. K., & Jernigan, R. L. (2018). Protein dynamic communities from elastic network models align closely to the communities defined by molecular dynamics. PLoS One, 13(6), e0199225. https://doi.org/10.1371/journal.pone.0199225
   PubMed Web of Science ®Google Scholar
• Mullard, A. (2018). Can innate immune system targets turn up the heat on 'cold' tumours? Nature Reviews. Drug Discovery, 17(1), 3–5. https://doi.org/10.1038/nrd.2017.264
   PubMed Web of Science ®Google Scholar
• Murakami, Y., Tripathi, L. P., Prathipati, P., & Mizuguchi, K. (2017). Network analysis and in silico prediction of protein-protein interactions with applications in drug discovery. Current Opinion in Structural Biology, 44, 134–142. https://doi.org/10.1016/j.sbi.2017.02.005
   PubMed Web of Science ®Google Scholar
• Novotná, B., Vaneková, L., Zavřel, M., Buděšínský, M., Dejmek, M., Smola, M., Gutten, O., Tehrani, Z. A., Pimková Polidarová, M., Brázdová, A., Liboska, R., Štěpánek, I., Vavřina, Z., Jandušík, T., Nencka, R., Rulíšek, L., Bouřa, E., Brynda, J., Páv, O., & Birkuš, G. (2019). Enzymatic preparation of 2'-5',3'-5'-cyclic dinucleotides, their binding properties to stimulator of interferon genes adaptor protein, and structure/activity correlations. Journal of Medicinal Chemistry, 62(23), 10676–10690. https://doi.org/10.1021/acs.jmedchem.9b01062
   PubMed Web of Science ®Google Scholar
• Pan, B. S., Perera, S. A., Piesvaux, J. A., Presland, J. P., Schroeder, G. K., Cumming, J. N., Trotter, B. W., Altman, M. D., Buevich, A. V., Cash, B., Cemerski, S., Chang, W., Chen, Y., Dandliker, P. J., Feng, G., Haidle, A., Henderson, T., Jewell, J., Kariv, I., … Addona, G. H. (2020). An orally available non-nucleotide STING agonist with antitumor activity. Science, 369(6506), eaba6098. https://doi.org/10.1126/science.aba6098
   PubMed Web of Science ®Google Scholar
• Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004). UCSF Chimera-a visualization system for exploratory research and analysis. Journal of Computational Chemistry, 25(13), 1605–1612. https://doi.org/10.1002/jcc.20084
   PubMed Web of Science ®Google Scholar
• Plattner, N., & Noe, F. (2015). Protein conformational plasticity and complex ligand-binding kinetics explored by atomistic simulations and Markov models. Nature Communications, 6, 7653. https://doi.org/10.1038/ncomms8653
   PubMed Web of Science ®Google Scholar
• Ramanjulu, J. M., Pesiridis, G. S., Yang, J., Concha, N., Singhaus, R., Zhang, S. Y., Tran, J. L., Moore, P., Lehmann, S., Eberl, H. C., Muelbaier, M., Schneck, J. L., Clemens, J., Adam, M., Mehlmann, J., Romano, J., Morales, A., Kang, J., Leister, L., … Bertin, J. (2018). Design of amidobenzimidazole STING receptor agonists with systemic activity. Nature, 564(7736), 439–443. https://doi.org/10.1038/s41586-018-0705-y
   PubMed Web of Science ®Google Scholar
• Roe, D. R., & Cheatham, T. E. 3rd, (2013). PTRAJ and CPPTRAJ: Software for processing and analysis of molecular dynamics trajectory data. Journal of Chemical Theory and Computation, 9(7), 3084–3095. https://doi.org/10.1021/ct400341p
   PubMed Web of Science ®Google Scholar
• Scherer, M. K., Trendelkamp-Schroer, B., Paul, F., Perez-Hernandez, G., Hoffmann, M., Plattner, N., Wehmeyer, C., Prinz, J. H., & Noe, F. (2015). PyEMMA 2: A software package for estimation, validation, and analysis of Markov Models. Journal of Chemical Theory and Computation, 11(11), 5525–5542. https://doi.org/10.1021/acs.jctc.5b00743
   PubMed Web of Science ®Google Scholar
• Schiebel, J., Gaspari, R., Wulsdorf, T., Ngo, K., Sohn, C., Schrader, T. E., Cavalli, A., Ostermann, A., Heine, A., & Klebe, G. (2018). Intriguing role of water in protein-ligand binding studied by neutron crystallography on trypsin complexes. Nature Communications, 9(1), 3559. https://doi.org/10.1038/s41467-018-05769-2
   PubMed Web of Science ®Google Scholar
• Sethi, A., Eargle, J., Black, A. A., & Luthey-Schulten, Z. (2009). Dynamical networks in tRNA:protein complexes. Proceedings of the National Academy of Sciences of the United States of America, 106(16), 6620–6625. https://doi.org/10.1073/pnas.0810961106
   PubMed Web of Science ®Google Scholar
• Shang, G., Zhang, C., Chen, Z. J., Bai, X. C., & Zhang, X. (2019). Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP. Nature, 567(7748), 389–393. https://doi.org/10.1038/s41586-019-0998-5
   PubMed Web of Science ®Google Scholar
• Shang, G., Zhu, D., Li, N., Zhang, J., Zhu, C., Lu, D., Liu, C., Yu, Q., Zhao, Y., Xu, S., & Gu, L. (2012). Crystal structures of STING protein reveal basis for recognition of cyclic di-GMP. Nature Structural & Molecular Biology, 19(7), 725–727. https://doi.org/10.1038/nsmb.2332
   PubMed Web of Science ®Google Scholar
• Shu, C., Yi, G., Watts, T., Kao, C. C., & Li, P. (2012). Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic dinucleotide recognition by the immune system. Nature Structural & Molecular Biology, 19(7), 722–724. https://doi.org/10.1038/nsmb.2331
   PubMed Web of Science ®Google Scholar
• Siu, T., Altman, M. D., Baltus, G. A., Childers, M., Ellis, J. M., Gunaydin, H., Hatch, H., Ho, T., Jewell, J., Lacey, B. M., Lesburg, C. A., Pan, B. S., Sauvagnat, B., Schroeder, G. K., & Xu, S. (2019). Discovery of a Novel cGAMP competitive ligand of the inactive form of STING. ACS Medicinal Chemistry Letters, 10(1), 92–97. https://doi.org/10.1021/acsmedchemlett.8b00466
   PubMed Web of Science ®Google Scholar
• Smola, M., Birkus, G., & Boura, E. (2019). No magnesium is needed for binding of the stimulator of interferon genes to cyclic dinucleotides. Acta Crystallographica. Section F, Structural Biology Communications, 75(Pt 9), 593–598. https://doi.org/10.1107/S2053230X19010999
   PubMedGoogle Scholar
• Smola, M., Gutten, O., Dejmek, M., Kozisek, M., Evangelidis, T., Tehrani, Z. A., Novotna, B., Nencka, R., Birkus, G., Rulisek, L., & Boura, E. (2021). Ligand strain and its conformational complexity is a major factor determining binding of cyclic dinucleotides to STING Protein. Angewandte Chemie International Edition, 60(18), 10172–10178.
   PubMed Web of Science ®Google Scholar
• Stetz, G., & Verkhivker, G. M. (2017). Computational analysis of residue interaction networks and coevolutionary relationships in the Hsp70 Chaperones: A community-hopping model of allosteric regulation and communication. PLoS Computational Biology, 13(1), e1005299. https://doi.org/10.1371/journal.pcbi.1005299
   PubMed Web of Science ®Google Scholar
• Sultan, M. M., Denny, R. A., Unwalla, R., Lovering, F., & Pande, V. S. (2017). Millisecond dynamics of BTK reveal kinome-wide conformational plasticity within the apo kinase domain. Scientific Reports, 7(1), 15604. https://doi.org/10.1038/s41598-017-10697-0
   PubMedGoogle Scholar
• UniProt, C. (2019). UniProt: A worldwide hub of protein knowledge. Nucleic Acids Research. , 47(D1), D506–D515.
   PubMed Web of Science ®Google Scholar
• Vavřina, Z., Gutten, O., Smola, M., Zavřel, M., Aliakbar Tehrani, Z., Charvát, V., Kožíšek, M., Boura, E., Birkuš, G., & Rulíšek, L. (2021). Protein-ligand interactions in the STING binding site probed by rationally designed single-point mutations: Experiment and Theory. Biochemistry, 60(8), 607–620. https://doi.org/10.1021/acs.biochem.0c00949
   PubMed Web of Science ®Google Scholar
• Wang, J., Wang, W., Kollman, P. A., & Case, D. A. (2006). Automatic atom type and bond type perception in molecular mechanical calculations. Journal of Molecular Graphics & Modelling, 25(2), 247–260. https://doi.org/10.1016/j.jmgm.2005.12.005
   PubMed Web of Science ®Google Scholar
• Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A., & Case, D. A. (2004). Development and testing of a general amber force field. Journal of Computational Chemistry, 25(9), 1157–1174. https://doi.org/10.1002/jcc.20035
   PubMed Web of Science ®Google Scholar
• Webb, B., & Sali, A. (2016). Comparative protein structure modeling using MODELLER. Curr Protoc Bioinformatics, 54, 5 6 1–5 6 37.
   PubMedGoogle Scholar
• Wu, J. J., Zhao, L., Hu, H. G., Li, W. H., & Li, Y. M. (2020). Agonists and inhibitors of the STING pathway: Potential agents for immunotherapy. Medicinal Research Reviews, 40(3), 1117–1141. https://doi.org/10.1002/med.21649
   PubMed Web of Science ®Google Scholar
• Yi, G., Brendel, V. P., Shu, C., Li, P., Palanathan, S., & Cheng Kao, C. (2013). Single nucleotide polymorphisms of human STING can affect innate immune response to cyclic dinucleotides. PLoS One, 8(10), e77846. https://doi.org/10.1371/journal.pone.0077846
   PubMed Web of Science ®Google Scholar
• Zhang, C., Shang, G., Gui, X., Zhang, X., Bai, X. C., & Chen, Z. J. (2019). Structural basis of STING binding with and phosphorylation by TBK1. Nature, 567(7748), 394–398. https://doi.org/10.1038/s41586-019-1000-2
   PubMed Web of Science ®Google Scholar
• Zhang, X., Shi, H., Wu, J., Zhang, X., Sun, L., Chen, C., & Chen, Z. J. (2013). Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Molecular Cell, 51(2), 226–235. https://doi.org/10.1016/j.molcel.2013.05.022
   PubMed Web of Science ®Google Scholar
• Zhong, B., Yang, Y., Li, S., Wang, Y. Y., Li, Y., Diao, F., Lei, C., He, X., Zhang, L., Tien, P., & Shu, H. B. (2008). The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity, 29(4), 538–550. https://doi.org/10.1016/j.immuni.2008.09.003
   PubMed Web of Science ®Google Scholar