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The protozoan parasite Giardia lamblia is the causative agent of giardiasis, a neglected infectious disease in humans. In this study, we used a bioinformatics approach to examine the structural features of GTOR, a G. lamblia TOR-like protein, and predict functional associations. Our findings confirmed that it shares significant similarities with functional TOR kinases, including a binding domain for the FKBP-rapamycin complex and a kinase domain resembling that of phosphatidylinositol 3-kinase-related kinases. In addition, it can form multiprotein complexes such as TORC1 and TORC2. These results provide valuable insights into the structure\u2013function relationship of GTOR, highlighting its potential as a molecular target for controlling G. lamblia cell proliferation. Furthermore, our study represents a step toward rational drug design for specific anti-giardiasis therapeutic agents.<\/jats:p>","DOI":"10.3390\/ijms241511992","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T01:27:46Z","timestamp":1690421266000},"page":"11992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Structural Insights into the Giardia lamblia Target of Rapamycin Homolog: A Bioinformatics Approach"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8303-6305","authenticated-orcid":false,"given":"Patricia L. 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Mol. Biol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cell.2012.03.017","article-title":"MTOR Signaling in Growth Control and Disease","volume":"149","author":"Laplante","year":"2012","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1534\/genetics.111.133363","article-title":"Target of Rapamycin (TOR) in Nutrient Signaling and Growth Control","volume":"189","author":"Loewith","year":"2011","journal-title":"Genetics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12574","DOI":"10.1073\/pnas.91.26.12574","article-title":"RAPT1, a Mammalian Homolog of Yeast Tor, Interacts with the FKBP12\/Rapamycin Complex","volume":"91","author":"Chiu","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1126\/science.273.5272.239","article-title":"Structure of the FKBP12-Rapamycin Complex Interacting with Binding Domain of Human FRAP","volume":"273","author":"Choi","year":"1996","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4715","DOI":"10.1021\/ja043277y","article-title":"Characterization of the FKBP\u00b7Rapamycin\u00b7FRB Ternary Complex","volume":"127","author":"Banaszynski","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1097\/TP.0000000000001806","article-title":"MTOR Inhibition Role in Cellular Mechanisms","volume":"102","author":"Zaza","year":"2018","journal-title":"Transplantation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpara.2018.07.003","article-title":"Giardia: An under-Reported Foodborne Parasite","volume":"49","author":"Ryan","year":"2019","journal-title":"Int. J. Parasitol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hajare, S.T., Chekol, Y., and Chauhan, N.M. (2022). Assessment of Prevalence of Giardia lamblia Infection and Its Associated Factors among Government Elementary School Children from Sidama Zone, SNNPR, Ethiopia. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0264812"},{"key":"ref_10","unstructured":"Rumsey, P., and Waseem, M. (2022). StatPearls, StatPearls Publishing."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Waldram, A., Vivancos, R., Hartley, C., and Lamden, K. (2017). Prevalence of Giardia Infection in Households of Giardia Cases and Risk Factors for Household Transmission. BMC Infect. Dis., 17.","DOI":"10.1186\/s12879-017-2586-3"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.pt.2006.02.015","article-title":"Giardia and Cryptosporidium Join the \u2018Neglected Diseases Initiative\u2019","volume":"22","author":"Savioli","year":"2006","journal-title":"Trends Parasitol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Solaymani-Mohammadi, S., Genkinger, J.M., Loffredo, C.A., and Singer, S.M. (2010). A Meta-Analysis of the Effectiveness of Albendazole Compared with Metronidazole as Treatments for Infections with Giardia duodenalis. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000682"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Granados, C.E., Reveiz, L., Uribe, L.G., and Criollo, C.P. (2012). Drugs for Treating Giardiasis. Cochrane Database Syst. Rev.","DOI":"10.1002\/14651858.CD007787.pub2"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.2147\/IDR.S141468","article-title":"Treatment-Refractory Giardiasis: Challenges and Solutions","volume":"11","author":"Lalle","year":"2018","journal-title":"Infect. Drug Resist."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"571104","DOI":"10.3389\/fmicb.2020.571104","article-title":"Recirculation of Giardia lamblia Assemblage A After Metronidazole Treatment in an Area With Assemblages A, B, and E Sympatric Circulation","volume":"11","author":"Fantinatti","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1128\/CMR.14.1.150-164.2001","article-title":"Drug Targets and Mechanisms of Resistance in the Anaerobic Protozoa","volume":"14","author":"Upcroft","year":"2001","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1097\/MCC.0b013e32830f1dd5","article-title":"Novel Strategies to Combat Bacterial Virulence: Curr","volume":"14","author":"Lynch","year":"2008","journal-title":"Opin. Crit. Care"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/s41579-022-00797-8","article-title":"Author Correction: Anti-Trypanosomatid Drug Discovery: Progress and Challenges","volume":"20","author":"Wyllie","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1007\/s00438-015-1056-0","article-title":"Evolutionary Conservation of TORC1 Components, TOR, Raptor, and LST8, between Rice and Yeast","volume":"290","author":"Maegawa","year":"2015","journal-title":"Mol. Genet. Genom."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3359","DOI":"10.1093\/bioinformatics\/btv362","article-title":"IBS: An Illustrator for the Presentation and Visualization of Biological Sequences","volume":"31","author":"Liu","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4947","DOI":"10.1073\/pnas.92.11.4947","article-title":"Identification of an 11-KDa FKBP12-Rapamycin-Binding Domain within the 289-KDa FKBP12-Rapamycin-Associated Protein and Characterization of a Critical Serine Residue","volume":"92","author":"Chen","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nature12122","article-title":"MTOR Kinase Structure, Mechanism and Regulation","volume":"497","author":"Yang","year":"2013","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/sj.onc.1210693","article-title":"Structural Characterization of the Interaction of MTOR with Phosphatidic Acid and a Novel Class of Inhibitor: Compelling Evidence for a Central Role of the FRB Domain in Small Molecule-Mediated Regulation of MTOR","volume":"27","author":"Veverka","year":"2008","journal-title":"Oncogene"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/82_2010_64","article-title":"New Inhibitors of the PI3K-Akt-MTOR Pathway: Insights into MTOR Signaling from a New Generation of Tor Kinase Domain Inhibitors (TORKinibs)","volume":"Volume 347","author":"Rommel","year":"2010","journal-title":"Phosphoinositide 3-Kinase in Health and Disease"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1111\/bcp.12893","article-title":"New Perspectives on MTOR Inhibitors (Rapamycin, Rapalogs and TORKinibs) in Transplantation: MTOR Complex Inhibition in Transplantation","volume":"82","author":"Waldner","year":"2016","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1186\/s12935-022-02706-8","article-title":"Recent Advances and Limitations of MTOR Inhibitors in the Treatment of Cancer","volume":"22","author":"Ali","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"819128","DOI":"10.3389\/fonc.2022.819128","article-title":"PI3K\/Akt\/MTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?","volume":"12","author":"Peng","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"875372","DOI":"10.3389\/fphar.2022.875372","article-title":"Recent Advances in Dual PI3K\/MTOR Inhibitors for Tumour Treatment","volume":"13","author":"Wu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.ijpara.2005.11.003","article-title":"Peptidyl-Prolyl Cis\u2013Trans Isomerases (Immunophilins) and Their Roles in Parasite Biochemistry, Host\u2013Parasite Interaction and Antiparasitic Drug Action","volume":"36","author":"Bell","year":"2006","journal-title":"Int. J. Parasitol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9622","DOI":"10.1021\/acs.jmedchem.6b00411","article-title":"Peptidyl-Proline Isomerases (PPIases): Targets for Natural Products and Natural Product-Inspired Compounds: Miniperspective","volume":"59","author":"Dunyak","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"MTOR Signaling in Growth, Metabolism, and Disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1042\/BST0390431","article-title":"MTOR Signalling in Health and Disease","volume":"39","author":"Proud","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.tcb.2015.10.003","article-title":"TOR Complexes and the Maintenance of Cellular Homeostasis","volume":"26","author":"Eltschinger","year":"2016","journal-title":"Trends Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3389\/fcell.2017.00061","article-title":"The TOR Signaling Pathway in Spatial and Temporal Control of Cell Size and Growth","volume":"5","author":"Gonzalez","year":"2017","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Conciatori, F., Ciuffreda, L., Bazzichetto, C., Falcone, I., Pilotto, S., Bria, E., Cognetti, F., and Milella, M. (2018). MTOR Cross-Talk in Cancer and Potential for Combination Therapy. Cancers, 10.","DOI":"10.3390\/cancers10010023"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Tafur, L., Kefauver, J., and Loewith, R. (2020). Structural Insights into TOR Signaling. Genes, 11.","DOI":"10.3390\/genes11080885"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13578-020-00396-1","article-title":"MTOR Signaling Pathway and MTOR Inhibitors in Cancer: Progress and Challenges","volume":"10","author":"Zou","year":"2020","journal-title":"Cell Biosci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mao, B., Zhang, Q., Ma, L., Zhao, D.-S., Zhao, P., and Yan, P. (2022). Overview of Research into MTOR Inhibitors. Molecules, 27.","DOI":"10.3390\/molecules27165295"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Yu, J.J., and Goncharova, E.A. (2022). MTOR Signaling Network in Cell Biology and Human Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232416142"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"129859","DOI":"10.1016\/j.bbagen.2021.129859","article-title":"A Myeloid Leukemia Factor Homolog Involved in Encystation-Induced Protein Metabolism in Giardia lamblia","volume":"1865","author":"Wu","year":"2021","journal-title":"Biochim. Biophys. Acta BBA\u2014Gen. Subj."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"The UniProt Consortium, Bateman, A., Martin, M.-J., Orchard, S., Magrane, M., Agivetova, R., Ahmad, S., Alpi, E., Bowler-Barnett, E.H., and Britto, R. (2021). UniProt: The Universal Protein Knowledgebase in 2021. Nucleic Acids Res., 49, D480\u2013D489.","DOI":"10.1093\/nar\/gkaa1100"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"W216","DOI":"10.1093\/nar\/gkab225","article-title":"Expasy, the Swiss Bioinformatics Resource Portal, as Designed by Its Users","volume":"49","author":"Duvaud","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1093\/bib\/3.3.265","article-title":"PROSITE: A Documented Database Using Patterns and Profiles as Motif Descriptors","volume":"3","author":"Sigrist","year":"2002","journal-title":"Brief. Bioinform."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"W362","DOI":"10.1093\/nar\/gkl124","article-title":"ScanProsite: Detection of PROSITE Signature Matches and ProRule-Associated Functional and Structural Residues in Proteins","volume":"34","author":"Sigrist","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"D344","DOI":"10.1093\/nar\/gks1067","article-title":"New and Continuing Developments at PROSITE","volume":"41","author":"Sigrist","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1006\/jmbi.2000.3684","article-title":"Homology-Based Method for Identification of Protein Repeats Using Statistical Significance Estimates","volume":"298","author":"Andrade","year":"2000","journal-title":"J. Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"W327","DOI":"10.1093\/nar\/gkh454","article-title":"CD-Search: Protein Domain Annotations on the Fly","volume":"32","author":"Bryant","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"D265","DOI":"10.1093\/nar\/gkz991","article-title":"CDD\/SPARCLE: The Conserved Domain Database in 2020","volume":"48","author":"Lu","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"D412","DOI":"10.1093\/nar\/gkaa913","article-title":"Pfam: The Protein Families Database in 2021","volume":"49","author":"Mistry","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/msb.2011.75","article-title":"Fast, Scalable Generation of High-quality Protein Multiple Sequence Alignments Using Clustal Omega","volume":"7","author":"Sievers","year":"2011","journal-title":"Mol. Syst. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1016\/j.jmb.2017.12.007","article-title":"A Completely Reimplemented MPI Bioinformatics Toolkit with a New HHpred Server at Its Core","volume":"430","author":"Zimmermann","year":"2018","journal-title":"J. Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nmeth.3213","article-title":"The I-TASSER Suite: Protein Structure and Function Prediction","volume":"12","author":"Yang","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"W174","DOI":"10.1093\/nar\/gkv342","article-title":"I-TASSER Server: New Development for Protein Structure and Function Predictions","volume":"43","author":"Yang","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"W408","DOI":"10.1093\/nar\/gkz322","article-title":"IntFOLD: An Integrated Web Resource for High Performance Protein Structure and Function Prediction","volume":"47","author":"McGuffin","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.jsb.2011.09.006","article-title":"UCSF Chimera, MODELLER, and IMP: An Integrated Modeling System","volume":"179","author":"Yang","year":"2012","journal-title":"J. Struct. Biol."},{"key":"ref_57","first-page":"39","article-title":"Protein Structure Modeling with MODELLER","volume":"Volume 1654","author":"Kaufmann","year":"2014","journal-title":"Functional Genomics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly Accurate Protein Structure Prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10696","DOI":"10.1038\/s41598-022-14382-9","article-title":"AlphaFold2 Models Indicate That Protein Sequence Determines Both Structure and Dynamics","volume":"12","author":"Guo","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/978-1-4939-7000-1_24","article-title":"Stereochemistry and Validation of Macromolecular Structures","volume":"Volume 1607","author":"Wlodawer","year":"2017","journal-title":"Protein Crystallography"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1016\/S0969-2126(96)00147-5","article-title":"Phi\/Psi-Chology: Ramachandran Revisited","volume":"4","author":"Kleywegt","year":"1996","journal-title":"Structure"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"W375","DOI":"10.1093\/nar\/gkm216","article-title":"MolProbity: All-Atom Contacts and Structure Validation for Proteins and Nucleic Acids","volume":"35","author":"Davis","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1016\/j.bpj.2011.10.024","article-title":"Improving the Physical Realism and Structural Accuracy of Protein Models by a Two-Step Atomic-Level Energy Minimization","volume":"101","author":"Xu","year":"2011","journal-title":"Biophys. J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1016\/j.str.2011.09.022","article-title":"Atomic-Level Protein Structure Refinement Using Fragment-Guided Molecular Dynamics Conformation Sampling","volume":"19","author":"Zhang","year":"2011","journal-title":"Structure"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: A Program to Check the Stereochemical Quality of Protein Structures","volume":"26","author":"Laskowski","year":"1993","journal-title":"J. Appl. Crystallogr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/356083a0","article-title":"Assessment of Protein Models with Three-Dimensional Profiles","volume":"356","author":"Bowie","year":"1992","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1002\/pro.5560020916","article-title":"Verification of Protein Structures: Patterns of Nonbonded Atomic Interactions","volume":"2","author":"Colovos","year":"1993","journal-title":"Protein Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"W407","DOI":"10.1093\/nar\/gkm290","article-title":"ProSA-Web: Interactive Web Service for the Recognition of Errors in Three-Dimensional Structures of Proteins","volume":"35","author":"Wiederstein","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1107\/S0907444909042073","article-title":"MolProbity: All-Atom Structure Validation for Macromolecular Crystallography","volume":"66","author":"Chen","year":"2010","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/pro.3330","article-title":"MolProbity: More and Better Reference Data for Improved All-Atom Structure Validation","volume":"27","author":"Williams","year":"2018","journal-title":"Protein Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A Visualization System for Exploratory Research and Analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"W303","DOI":"10.1093\/nar\/gkt498","article-title":"The FunFOLD2 Server for the Prediction of Protein\u2013Ligand Interactions","volume":"41","author":"Roche","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1093\/bioinformatics\/btt447","article-title":"Protein\u2013Ligand Binding Site Recognition Using Complementary Binding-Specific Substructure Comparison and Sequence Profile Alignment","volume":"29","author":"Yang","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"D1096","DOI":"10.1093\/nar\/gks966","article-title":"BioLiP: A Semi-Manually Curated Database for Biologically Relevant Ligand\u2013Protein Interactions","volume":"41","author":"Yang","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"W345","DOI":"10.1093\/nar\/gkz424","article-title":"PrankWeb: A Web Server for Ligand Binding Site Prediction and Visualization","volume":"47","author":"Jendele","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"W431","DOI":"10.1093\/nar\/gkab314","article-title":"Mol* Viewer: Modern Web App for 3D Visualization and Analysis of Large Biomolecular Structures","volume":"49","author":"Sehnal","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1093\/protein\/8.2.127","article-title":"LIGPLOT: A Program to Generate Schematic Diagrams of Protein-Ligand Interactions","volume":"8","author":"Wallace","year":"1995","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1021\/ci200227u","article-title":"LigPlot+: Multiple Ligand\u2013Protein Interaction Diagrams for Drug Discovery","volume":"51","author":"Laskowski","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"W530","DOI":"10.1093\/nar\/gkab294","article-title":"PLIP 2021: Expanding the Scope of the Protein\u2013Ligand Interaction Profiler to DNA and RNA","volume":"49","author":"Adasme","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1093\/nar\/gkg034","article-title":"STRING: A Database of Predicted Functional Associations between Proteins","volume":"31","author":"Huynen","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING V11: Protein\u2013Protein Association Networks with Increased Coverage, Supporting Functional Discovery in Genome-Wide Experimental Datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"D344","DOI":"10.1093\/nar\/gkaa977","article-title":"The InterPro Protein Families and Domains Database: 20 Years On","volume":"49","author":"Blum","year":"2021","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/11992\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:19:34Z","timestamp":1760127574000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/11992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,26]]},"references-count":83,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["ijms241511992"],"URL":"https:\/\/doi.org\/10.3390\/ijms241511992","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,26]]}}}