Screening of novel and selective inhibitors for neuronal nitric oxide synthase (nNOS) via structure-based drug design techniques

References

• Alderton, W. K., Cooper, C. E., & Knowles, R. G. (2001). Nitric oxide synthases: structure, function, and inhibition. The Biochemical Journal, 357(Pt 3), 593–615. https://doi.org/10.1042/0264-6021:3570593
   PubMed Web of Science ®Google Scholar
• Ali, S. A., Hassan, M. I., Islam, A., & Ahmad, F. (2014). A review of methods available to estimate solvent-accessible surface areas of soluble proteins in the folded and unfolded states. Current Protein & Peptide Science, 15(5), 456–476. https://doi.org/10.2174/1389203715666140327114232
   PubMed Web of Science ®Google Scholar
• Assmann, T. S., Brondani, L. A., Bouças, A. P., Rheinheimer, J., de Souza, B. M., Canani, L. H., Bauer, A. C., & Crispim, D. (2016). Nitric oxide levels in patients with diabetes mellitus: A systematic review and meta-analysis. Nitric Oxide, 61, 1–9. https://doi.org/10.1016/j.niox.2016.09.009
   PubMed Web of Science ®Google Scholar
• Bianchi, V., Gherardini, P. F., Helmer-Citterich, M., & Ausiello, G. (2012). Identification of binding pockets in protein structures using a knowledge-based potential derived from local structural similarities. BMC Bioinformatics, 13(Suppl 4), S17. https://doi.org/10.1186/1471-2105-13-S4-S17.[PMC][22536963
   PubMed Web of Science ®Google Scholar
• Bignon, E., Rizza, S., Filomeni, G., & Papaleo, E. (2019). Use of computational biochemistry for elucidating molecular mechanisms of nitric oxide synthase. Computational and Structural Biotechnology Journal, 17, 415–429. https://doi.org/10.1016/j.csbj.2019.03.011.[PMC][30996821
   PubMed Web of Science ®Google Scholar
• Bladowski, M., Gawrys, J., Gajecki, D., Szahidewicz-Krupska, E., Sawicz-Bladowska, A., & Doroszko, A. (2020). Role of the Platelets and Nitric Oxide Biotransformation in Ischemic Stroke: A Translative Review from Bench to Bedside. Oxidative Medicine and Cellular Longevity, 2020, 2979260. https://doi.org/10.1155/2020/2979260.[PMC][32908630
   PubMed Web of Science ®Google Scholar
• Bruckdorfer, R. (2005). The basics about nitric oxide. Molecular Aspects of Medicine, 26(1–2), 3–31. https://doi.org/10.1016/j.mam.2004.09.002.[PMC][15722113
   PubMedGoogle Scholar
• Caron, G., Ermondi, G., Gariboldi, M. B., Monti, E., Gabano, E., Ravera, M., & Osella, D. (2009). The relevance of polar surface area (PSA) in rationalizing biological properties of several cis-diamminemalonatoplatinum(II) derivatives. ChemMedChem, 4(10), 1677–1685. https://doi.org/10.1002/cmdc.200900224.[PMC][19637156
   PubMed Web of Science ®Google Scholar
• Cereto-Massagué, A., Guasch, L., Valls, C., Mulero, M., Pujadas, G., & Garcia-Vallvé, S. (2012). DecoyFinder: an easy-to-use python GUI application for building target-specific decoy sets. Bioinformatics, 28(12), 1661–1662. https://doi.org/10.1093/bioinformatics/bts249
   PubMed Web of Science ®Google Scholar
• Cinelli, M. A., Li, H., Chreifi, G., Poulos, T. L., & Silverman, R. B. (2017). Nitrile in the hole: Discovery of a small auxiliary pocket in neuronal nitric oxide synthase leading to the development of potent and selective 2-aminoquinoline inhibitors. Journal of Medicinal Chemistry, 60(9), 3958–3978. https://doi.org/10.1021/acs.jmedchem.7b00259
   PubMed Web of Science ®Google Scholar
• Correa-Aragunde, N., Foresi, N., & Lamattina, L. (2013). Structure diversity of nitric oxide synthases (NOS): the emergence of new forms in photosynthetic organisms. Frontiers in Plant Science, 4, 232. https://doi.org/10.3389/fpls.2013.00232
   PubMed Web of Science ®Google Scholar
• Daiber, A., Xia, N., Steven, S., Oelze, M., Hanf, A., Kröller-Schön, S., Münzel, T., & Li, H. (2019). New therapeutic implications of endothelial nitric oxide synthase (eNOS) function/dysfunction in cardiovascular diseases. International Journal of Molecular Sciences, 20(1), 187. https://doi.org/10.3390/ijms20010187
   PubMed Web of Science ®Google Scholar
• Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7, 42717. https://doi.org/10.1038/srep42717
   PubMed Web of Science ®Google Scholar
• Daneman, R., & Prat, A. (2015). The blood-brain barrier. Cold Spring Harbor Perspectives in Biology, 7(1), a020412. https://doi.org/10.1101/cshperspect.Å20412. https://doi.org/10.1101/cshperspect.a020412
   PubMed Web of Science ®Google Scholar
• Ding, Y., Tang, J., & Guo, F. (2017). Identification of protein-ligand binding sites by sequence information and ensemble classifier. Journal of Chemical Information and Modeling, 57(12), 3149–3161. https://doi.org/10.1021/acs.jcim.7b00307
   PubMed Web of Science ®Google Scholar
• Do, H. T., Li, H., Chreifi, G., Poulos, T. L., & Silverman, R. B. (2019). Optimization of blood-brain barrier permeability with potent and selective human neuronal nitric oxide synthase inhibitors having a 2-aminopyridine scaffold. Journal of Medicinal Chemistry, 62(5), 2690–2707. https://doi.org/10.1021/acs.jmedchem.8b02032
   PubMed Web of Science ®Google Scholar
• Do, H. T., Wang, H. Y., Li, H., Chreifi, G., Poulos, T. L., & Silverman, R. B. (2017). Improvement of cell permeability of human neuronal nitric oxide synthase inhibitors using potent and selective 2-aminopyridine-based scaffolds with a fluorobenzene linker. Journal of Medicinal Chemistry, 60(22), 9360–9375. https://doi.org/10.1021/acs.jmedchem.7b01356
   PubMed Web of Science ®Google Scholar
• Do, H. T., Wang, H. Y., Li, H., Chreifi, G., Poulos, T. L., & Silverman, R. B. (2019). Correction to improvement of cell permeability of human neuronal nitric oxide synthase inhibitors using potent and selective 2-aminopyridine-based scaffolds with a fluorobenzene linker. Journal of Medicinal Chemistry, 62(2), 1074. https://doi.org/10.1021/acs.jmedchem.8b01866
   PubMed Web of Science ®Google Scholar
• Eisenberg, D., Lüthy, R., & Bowie, J. U. (1997). VERIFY3D: assessment of protein models with three-dimensional profiles. Methods in Enzymology, 277, 396–404. https://doi.org/10.1016/s0076-6879(97)77022-8.[PMC][9379925
   PubMed Web of Science ®Google Scholar
• Ekins, S., Mestres, J., & Testa, B. (2007). In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling. British Journal of Pharmacology, 152(1), 9–20. https://doi.org/10.1038/sj.bjp.0707305
   PubMed Web of Science ®Google Scholar
• Emmerich, C. H., Gamboa, L. M., Hofmann, M., Bonin-Andresen, M., Arbach, O., Schendel, P., Gerlach, B., Hempel, K., Bespalov, A., Dirnagl, U., & Parnham, M. J. (2021). Improving target assessment in biomedical research: the GOT-IT recommendations. Nature Reviews. Drug Discovery, 20(1), 64–81. https://doi.org/10.1038/s41573-020-0087-3
   PubMed Web of Science ®Google Scholar
• Erijman, A., Rosenthal, E., & Shifman, J. M. (2014). How structure defines affinity in protein-protein interactions. PloS One, 9(10), e110085. https://doi.org/10.1371/journal.pone.0110085
   PubMed Web of Science ®Google Scholar
• Fedorov, R., Vasan, R., Ghosh, D. K., & Schlichting, I. (2004). Structures of nitric oxide synthase isoforms complexed with the inhibitor AR-R17477 suggest a rational basis for specificity and inhibitor design. Proceedings of the National Academy of Sciences of the United States of America, 101(16), 5892–5897. https://doi.org/10.1073/pnas.0306588101
   PubMed Web of Science ®Google Scholar
• Förstermann, U., & Kleinert, H. (1995). Nitric oxide synthase: expression and expressional control of the three isoforms. Naunyn-Schmiedeberg's Archives of Pharmacology, 352(4), 351–364. https://doi.org/10.1007/BF00172772
   PubMed Web of Science ®Google Scholar
• Förstermann, U., & Sessa, W. C. (2012). Nitric oxide synthases: regulation and function. European Heart Journal, 33(7), 829–837d. https://doi.org/10.1093/eurheartj/ehr304
   PubMed Web of Science ®Google Scholar
• Garcin, E. D., Arvai, A. S., Rosenfeld, R. J., Kroeger, M. D., Crane, B. R., Andersson, G., Andrews, G., Hamley, P. J., Mallinder, P. R., Nicholls, D. J., St-Gallay, S. A., Tinker, A. C., Gensmantel, N. P., Mete, A., Cheshire, D. R., Connolly, S., Stuehr, D. J., Aberg, A., Wallace, A. V., Tainer, J. A., … Getzoff, E. D. (2008). Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase. Nature Chemical Biology, 4(11), 700–707. https://doi.org/10.1038/nchembio.115
   PubMed Web of Science ®Google Scholar
• Ghafourifar, P., & Cadenas, E. (2005). Mitochondrial nitric oxide synthase. Trends in Pharmacological Sciences, 26(4), 190–195. https://doi.org/10.1016/j.tips.2005.02.005
   PubMed Web of Science ®Google Scholar
• Hollingsworth, S. A., & Karplus, P. A. (2010). A fresh look at the Ramachandran plot and the occurrence of standard structures in proteins. Biomolecular Concepts, 1(3–4), 271–283. https://doi.org/10.1515/BMC.2010.022
   PubMedGoogle Scholar
• Huang, H., Ji, H., Li, H., Jing, Q., Labby, K. J., Martásek, P., Roman, L. J., Poulos, T. L., & Silverman, R. B. (2012). Selective monocationic inhibitors of neuronal nitric oxide synthase. Binding mode insights from molecular dynamics simulations. Journal of the American Chemical Society, 134(28), 11559–11572. https://doi.org/10.1021/ja302269r
   PubMed Web of Science ®Google Scholar
• Ignarro, L. J. (2019). Nitric oxide is not just blowing in the wind. British Journal of Pharmacology, 176(2), 131–134. https://doi.org/10.1111/bph.14540
   PubMed Web of Science ®Google Scholar
• Ji, H., Tan, S., Igarashi, J., Li, H., Derrick, M., Martásek, P., Roman, L. J., Vásquez-Vivar, J., Poulos, T. L., & Silverman, R. B. (2009). Selective neuronal nitric oxide synthase inhibitors and the prevention of cerebral palsy. Annals of Neurology, 65(2), 209–217. https://doi.org/10.1002/ana.21555
   PubMed Web of Science ®Google Scholar
• Jing, Q., Li, H., Fang, J., Roman, L. J., Martásek, P., Poulos, T. L., & Silverman, R. B. (2013). In search of potent and selective inhibitors of neuronal nitric oxide synthase with more simple structures. Bioorganic & Medicinal Chemistry, 21(17), 5323–5331. https://doi.org/10.1016/j.bmc.2013.06.014
   PubMed Web of Science ®Google Scholar
• Jo, S., Kim, T., Iyer, V. G., & Im, W. (2008). CHARMM-GUI: a web-based graphical user interface for CHARMM. Journal of Computational Chemistry, 29(11), 1859–1865. https://doi.org/10.1002/jcc.20945
   PubMed Web of Science ®Google Scholar
• Knott, A. B., & Bossy-Wetzel, E. (2010). Impact of nitric oxide on metabolism in health and age-related disease. Diabetes, Obesity & Metabolism, 12(2), 126–133. https://doi.org/10.1111/j.1463-1326.2010.01267.x
   PubMedGoogle Scholar
• Ko, J., Park, H., Heo, L., & Seok, C. (2012). GalaxyWEB server for protein structure prediction and refinement. Nucleic Acids Research, 40(Web Server issue), W294–W297. https://doi.org/10.1093/nar/gks493
   PubMed Web of Science ®Google Scholar
• Koonin, E. V., & Galperin, M. Y. (2003). Sequence - Evolution - Function: Computational approaches in comparative genomics. Kluwer Academic.
   Google Scholar
• Kumar, C. V., Swetha, R. G., Anbarasu, A., & Ramaiah, S. (2014). Computational analysis reveals the association of threonine 118 methionine mutation in PMP22 resulting in CMT-1A. Advances in Bioinformatics, 2014, 502618. https://doi.org/10.1155/2014/502618
   PubMedGoogle Scholar
• Lee, S., Wang, C., Liu, H., Xiong, J., Jiji, R., Hong, X., Yan, X., Chen, Z., Hammel, M., Wang, Y., Dai, S., Wang, J., Jiang, C., & Zhang, G. (2017). Hydrogen bonds are a primary driving force for de novo protein folding. Acta Crystallographica. Section D, Structural Biology, 73(Pt 12), 955–969. (Retraction published Acta Crystallogr D Struct Biol. 2018 Apr 1;74(Pt 4):380) https://doi.org/10.1107/S2059798317015303
   PubMedGoogle Scholar
• Levinsson, A., Olin, A. C., Björck, L., Rosengren, A., & Nyberg, F. (2014). Nitric oxide synthase (NOS) single nucleotide polymorphisms are associated with coronary heart disease and hypertension in the INTERGENE study. Nitric Oxide: Biology and Chemistry, 39, 1–7. https://doi.org/10.1016/j.niox.2014.03.164
   PubMed Web of Science ®Google Scholar
• Li, H., Jamal, J., Delker, S., Plaza, C., Ji, H., Jing, Q., Huang, H., Kang, S., Silverman, R. B., & Poulos, T. L. (2014). The mobility of a conserved tyrosine residue controls isoform-dependent enzyme-inhibitor interactions in nitric oxide synthases. Biochemistry, 53(32), 5272–5279. https://doi.org/10.1021/bi500561h
   PubMed Web of Science ®Google Scholar
• Li, Q., & Shah, S. (2017). Structure-based virtual screening. Methods in Molecular Biology (Clifton, NY), 1558, 111–124. https://doi.org/10.1007/978-1-4939-6783-4_5
   PubMedGoogle Scholar
• Lin, J., Sahakian, D. C., de Morais, S. M., Xu, J. J., Polzer, R. J., & Winter, S. M. (2003). The role of absorption, distribution, metabolism, excretion and toxicity in drug discovery. Current Topics in Medicinal Chemistry, 3(10), 1125–1154. https://doi.org/10.2174/1568026033452096
   PubMed Web of Science ®Google Scholar
• Lindahl, E. R. (2008). Molecular dynamics simulations. Methods in Molecular Biology (Clifton, N.J.), 443, 3–23. https://doi.org/10.1007/978-1-59745-177-2_1
   PubMedGoogle Scholar
• Liu, X., Srinivasan, P., Collard, E., Grajdeanu, P., Zweier, J. L., & Friedman, A. (2008). Nitric oxide diffusion rate is reduced in the aortic wall. Biophysical Journal, 94(5), 1880–1889. https://doi.org/10.1529/biophysj.107.120626
   PubMed Web of Science ®Google Scholar
• Livingstone, C. D., & Barton, G. J. (1993). Protein sequence alignments: a strategy for the hierarchical analysis of residue conservation. Computer Applications in the Biosciences: CABIOS, 9(6), 745–756. https://doi.org/10.1093/bioinformatics/9.6.745
   PubMedGoogle Scholar
• Luiking, Y. C., Engelen, M. P., & Deutz, N. E. (2010). Regulation of nitric oxide production in health and disease. Current Opinion in Clinical Nutrition and Metabolic Care, 13(1), 97–104. https://doi.org/10.1097/MCO.0b013e328332f99d.[PMC][19841582
   PubMed Web of Science ®Google Scholar
• Marsh, N., & Marsh, A. (2000). A short history of nitroglycerine and nitric oxide in pharmacology and physiology. Clinical and Experimental Pharmacology & Physiology, 27(4), 313–319. https://doi.org/10.1046/j.1440-1681.2000.03240.x
   PubMed Web of Science ®Google Scholar
• Martínez, L. (2015). Automatic identification of mobile and rigid substructures in molecular dynamics simulations and fractional structural fluctuation analysis. PloS One, 10(3), e0119264. https://doi.org/10.1371/journal.pone.0119264
   PubMed Web of Science ®Google Scholar
• Martins, J. M., Ramos, R. M., Pimenta, A. C., & Moreira, I. S. (2014). Solvent-accessible surface area: How well can be applied to hot-spot detection? Proteins, 82(3), 479–490. https://doi.org/10.1002/prot.24413
   PubMed Web of Science ®Google Scholar
• Maveyraud, L., & Mourey, L. (2020). Protein X-ray crystallography and drug discovery. Molecules (Switzerland), 25(5), 1030. https://doi.org/10.3390/molecules25051030
   PubMed Web of Science ®Google Scholar
• Mohs, R. C., & Greig, N. H. (2017). Drug discovery and development: Role of basic biological research. Alzheimer's & Dementia (New York, NY), 3(4), 651–657. https://doi.org/10.1016/j.trci.2017.10.005
   PubMedGoogle Scholar
• Morgan, S., Grootendorst, P., Lexchin, J., Cunningham, C., & Greyson, D. (2011). The cost of drug development: a systematic review. Health Policy (Amsterdam, Netherlands), 100(1), 4–17. https://doi.org/10.1016/j.healthpol.2010.12.002
   PubMed Web of Science ®Google Scholar
• Morris, G. M., & Lim-Wilby, M. (2008). Molecular docking. Methods in Molecular Biology (Clifton, NJ), 443, 365–382. https://doi.org/10.1007/978-1-59745-177-2_19.
   PubMedGoogle Scholar
• Mukherjee, P., Cinelli, M. A., Kang, S., & Silverman, R. B. (2014). Development of nitric oxide synthase inhibitors for neurodegeneration and neuropathic pain. Chemical Society Reviews, 43(19), 6814–6838. https://doi.org/10.1039/c3cs60467e
   PubMed Web of Science ®Google Scholar
• Mukherjee, P., Li, H., Sevrioukova, I., Chreifi, G., Martásek, P., Roman, L. J., Poulos, T. L., & Silverman, R. B. (2015). Novel 2,4-disubstituted pyrimidines as potent, selective, and cell-permeable inhibitors of neuronal nitric oxide synthase. Journal of Medicinal Chemistry, 58(3), 1067–1088. https://doi.org/10.1021/jm501719e
   PubMed Web of Science ®Google Scholar
• Olesen, J. (2008). The role of nitric oxide (NO) in migraine, tension-type headache and cluster headache. Pharmacology & Therapeutics, 120(2), 157–171. https://doi.org/10.1016/j.pharmthera.2008.08.003
   PubMed Web of Science ®Google Scholar
• Pacher, P., Beckman, J. S., & Liaudet, L. (2007). Nitric oxide and peroxynitrite in health and disease. Physiological Reviews, 87(1), 315–424. https://doi.org/10.1152/physrev.00029.2006
   PubMed Web of Science ®Google Scholar
• Parasuraman, S. (2012). Protein data bank. Journal of Pharmacology & Pharmacotherapeutics, 3(4), 351–352. https://doi.org/10.4103/0976-500X.103704
   PubMedGoogle Scholar
• Pavanelli, W. R., Gutierrez, F. R., Silva, J. J., Costa, I. C., Menezes, M. C., Oliveira, F. J., Itano, E. N., & Watanabe, M. A. (2010). The effects of nitric oxide on the immune response during giardiasis. The Brazilian Journal of Infectious Diseases: An Official Publication of the Brazilian Society of Infectious Diseases, 14(6), 606–612. https://doi.org/10.1016/S1413-8670(10)70119-7
   PubMed Web of Science ®Google Scholar
• Pensa, A. V., Cinelli, M. A., Li, H., Chreifi, G., Mukherjee, P., Roman, L. J., Martásek, P., Poulos, T. L., & Silverman, R. B. (2017). Hydrophilic, potent, and selective 7-substituted 2-aminoquinolines as improved human neuronal nitric oxide synthase inhibitors. Journal of Medicinal Chemistry, 60(16), 7146–7165. https://doi.org/10.1021/acs.jmedchem.7b00835
   PubMed Web of Science ®Google Scholar
• Phillips, J. C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Chipot, C., Skeel, R. D., Kalé, L., & Schulten, K. (2005). Scalable molecular dynamics with NAMD. Journal of Computational Chemistry, 26(16), 1781–1802. https://doi.org/10.1002/jcc.20289
   PubMed Web of Science ®Google Scholar
• Picón-Pagès, P., Garcia-Buendia, J., & Muñoz, F. J. (2019). Functions and dysfunctions of nitric oxide in brain. Biochimica et Biophysica Acta. Molecular Basis of Disease, 1865(8), 1949–1967. https://doi.org/10.1016/j.bbadis.2018.11.007
   PubMed Web of Science ®Google Scholar
• Pitera, J. W. (2014). Expected distributions of root-mean-square positional deviations in proteins. The Journal of Physical Chemistry. B, 118(24), 6526–6530. https://doi.org/10.1021/jp412776d
   PubMed Web of Science ®Google Scholar
• Pontius, J., Richelle, J., & Wodak, S. J. (1996). Deviations from standard atomic volumes as a quality measure for protein crystal structures. Journal of Molecular Biology, 264(1), 121–136. https://doi.org/10.1006/jmbi.1996.0628
   PubMed Web of Science ®Google Scholar
• Poulos, T. L., & Li, H. (2017). Nitric oxide synthase and structure-based inhibitor design. Nitric Oxide : biology and Chemistry, 63, 68–77. https://doi.org/10.1016/j.niox.2016.11.004
   PubMed Web of Science ®Google Scholar
• Ruan, J., Xie, w., Hutchinson, N., Cho, H., Wolfe, G. C., & Nathan, C. (1996). Inducible nitric oxide synthase requires both the canonical calmodulin-binding domain and additional sequences in order to bind calmodulin and produce nitric oxide in the absence of free Ca2+. The Journal of Biological Chemistry, 271(37), 22679–22686. https://doi.org/10.1074/jbc.271.37.22679
   PubMed Web of Science ®Google Scholar
• Sargsyan, K., Grauffel, C., & Lim, C. (2017). How molecular size impacts RMSD applications in molecular dynamics simulations. Journal of Chemical Theory and Computation, 13(4), 1518–1524. https://doi.org/10.1021/acs.jctc.7b00028
   PubMed Web of Science ®Google Scholar
• Saxena, A. K., & Prathipati, P. (2006). Collection and preparation of molecular databases for virtual screening. SAR and QSAR in Environmental Research, 17(4), 371–392. https://doi.org/10.1080/10629360600884462
   PubMed Web of Science ®Google Scholar
• Schober, P., Boer, C., & Schwarte, L. A. (2018). Correlation Coefficients: Appropriate Use and Interpretation. Anesthesia and Analgesia, 126(5), 1763–1768. https://doi.org/10.1213/ANE.0000000000002864
   PubMed Web of Science ®Google Scholar
• Schulz, R., Kelm, M., & Heusch, G. (2004). Nitric oxide in myocardial ischemia/reperfusion injury. Cardiovascular Research, 61(3), 402–413. https://doi.org/10.1016/j.cardiores.2003.09.019
   PubMed Web of Science ®Google Scholar
• Sharma, J. N., Al-Omran, A., & Parvathy, S. S. (2007). Role of nitric oxide in inflammatory diseases. Inflammopharmacology, 15(6), 252–259. https://doi.org/10.1007/s10787-007-0013-x
   PubMedGoogle Scholar
• Shim, J., & Mackerell Jr, A. D. (2011). Computational ligand-based rational design: Role of conformational sampling and force fields in model development. MedChemComm, 2(5), 356–370. https://doi.org/10.1039/C1MD00044F
   PubMed Web of Science ®Google Scholar
• Sioud, M. (2007). Main approaches to target discovery and validation. Methods in Molecular Biology (Clifton, NJ), 360, 1–12. https://doi.org/10.1385/1-59745-165-7:1.
   PubMedGoogle Scholar
• Sterling, T., & Irwin, J. J. (2015). ZINC 15-ligand discovery for everyone. Journal of Chemical Information and Modeling, 55(11), 2324–2337. https://doi.org/10.1021/acs.jcim.5b00559
   PubMed Web of Science ®Google Scholar
• Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455–461. https://doi.org/10.1002/jcc.21334
   PubMed Web of Science ®Google Scholar
• Tuteja, N., Chandra, M., Tuteja, R., & Misra, M. K. (2004). Nitric oxide as a unique bioactive signaling messenger in physiology and pathophysiology. Journal of Biomedicine & Biotechnology, 2004(4), 227–237. https://doi.org/10.1155/S1110724304402034
   PubMedGoogle Scholar
• Umar, S., & van der Laarse, A. (2010). Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart. Molecular and Cellular Biochemistry, 333(1-2), 191–201. https://doi.org/10.1007/s11010-009-0219-x
   PubMed Web of Science ®Google Scholar
• Wang, X., Song, K., Li, L., & Chen, L. (2018). Structure-based drug design strategies and challenges. Current Topics in Medicinal Chemistry, 18(12), 998–1006. https://doi.org/10.2174/1568026618666180813152921
   PubMed Web of Science ®Google Scholar
• Wei, S., Brooks, C., & Frank, A. (2017). A rapid solvent accessible surface area estimator for coarse grained molecular simulations. Journal of Computational Chemistry, 38(15), 1270–1274. https://doi.org/10.1002/jcc.24709
   PubMed Web of Science ®Google Scholar
• Winkler, M. S., Kluge, S., Holzmann, M., Moritz, E., Robbe, L., Bauer, A., Zahrte, C., Priefler, M., Schwedhelm, E., Böger, R. H., Goetz, A. E., Nierhaus, A., & Zoellner, C. (2017). Markers of nitric oxide are associated with sepsis severity: an observational study. Critical Care, 21(1), 189. https://doi.org/10.1186/s13054-017-1782-2
   PubMedGoogle Scholar
• Xiang, Z. (2006). Advances in homology protein structure modeling. Current Protein & Peptide Science, 7(3), 217–227. https://doi.org/10.2174/138920306777452312
   PubMed Web of Science ®Google Scholar
• Xue, Q., Yan, Y., Zhang, R., & Xiong, H. (2018). Regulation of iNOS on immune cells and its role in diseases. International Journal of Molecular Sciences, 19(12), 3805. https://doi.org/10.3390/ijms19123805
   PubMed Web of Science ®Google Scholar
• Yu, W., & MacKerell, A. D. Jr(2017). Computer-aided drug design methods. Methods in Molecular Biology (Clifton, NJ), 1520, 85–106. https://doi.org/10.1007/978-1-4939-6634-9_5.
   PubMedGoogle Scholar
• Zhang, M. Q., & Wilkinson, B. (2007). Drug discovery beyond the 'rule-of-five'. Current Opinion in Biotechnology, 18(6), 478–488. https://doi.org/10.1016/j.copbio.2007.10.005
   PubMed Web of Science ®Google Scholar