{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:14:00Z","timestamp":1790957640641,"version":"4.1.0"},"reference-count":87,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["DELGEME grant 107740\/Z\/15\/Z"],"award-info":[{"award-number":["DELGEME grant 107740\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DELTAS Africa Initiative","award":["107740\/Z\/15\/Z"],"award-info":[{"award-number":["107740\/Z\/15\/Z"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Malaria elimination can benefit from time and cost-efficient approaches for antimalarials such as drug repurposing. In this work, 796 DrugBank compounds were screened against 36\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    targets using QuickVina-W. Hits were selected after rescoring using GRaph Interaction Matching (GRIM) and ligand efficiency metrics: surface efficiency index (SEI), binding efficiency index (BEI) and lipophilic efficiency (LipE). They were further evaluated in Molecular dynamics (MD). Twenty-five protein\u2013ligand complexes were finally retained from the 28,656 (36\u2009\u00d7\u2009796) dockings. Hit GRIM scores (0.58 to 0.78) showed their molecular interaction similarity to co-crystallized ligands. Minimum LipE (3), SEI (23) and BEI (7) were in at least acceptable thresholds for hits. Binding energies ranged from \u22126 to \u221211\u00a0kcal\/mol. Ligands showed stability in MD simulation with good hydrogen bonding and favorable protein\u2013ligand interactions energy (the poorest being \u2212140.12\u00a0kcal\/mol). In vitro testing showed 4 active compounds with two having IC\n                    <jats:sub>50<\/jats:sub>\n                    values in the single-digit \u03bcM range.\n                  <\/jats:p>","DOI":"10.1038\/s41598-020-80722-2","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T06:11:08Z","timestamp":1610604668000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Potential repurposing of four FDA approved compounds with antiplasmodial activity identified through proteome scale computational drug discovery and in vitro assay"],"prefix":"10.1038","volume":"11","author":[{"given":"Bakary N\u2019tji","family":"Diallo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarryn","family":"Swart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich C.","family":"Hoppe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zlem","family":"Tastan Bishop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Lobb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"key":"80722_CR1","unstructured":"World Health Organization. WHO Malaria report 2019. Malaria report 2019 https:\/\/www.who.int\/publications-detail\/world-malaria-report-2019 (2019)."},{"key":"80722_CR2","doi-asserted-by":"publisher","unstructured":"Lunev, S., Batista, F. A., Bosch, S. S., Wrenger, C. & Groves, M. R. Identification and Validation of Novel Drug Targets for the Treatment of Plasmodium falciparum Malaria: New Insights. Current Topics in Malaria (InTech, 2016). https:\/\/doi.org\/10.5772\/65659.","DOI":"10.5772\/65659"},{"key":"80722_CR3","doi-asserted-by":"publisher","first-page":"e1002380","DOI":"10.1371\/journal.pbio.1002380","volume":"14","author":"J Hemingway","year":"2016","unstructured":"Hemingway, J. et al. Tools and strategies for malaria control and elimination: what do we need to achieve a grand convergence in Malaria?. PLoS Biol. 14, e1002380 (2016).","journal-title":"PLoS Biol."},{"key":"80722_CR4","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.1039\/c2cs35357a","volume":"42","author":"D-L Ma","year":"2013","unstructured":"Ma, D.-L., Chan, D.S.-H. & Leung, C.-H. Drug repositioning by structure-based virtual screening. Chem. Soc. Rev. 42, 2130 (2013).","journal-title":"Chem. Soc. Rev."},{"key":"80722_CR5","doi-asserted-by":"publisher","first-page":"363","DOI":"10.2174\/1570193X13666160728121823","volume":"13","author":"P Vora","year":"2016","unstructured":"Vora, P., Somani, R. & Jain, M. Drug repositioning: an approach for drug discovery. Mini. Rev. Org. Chem. 13, 363\u2013376 (2016).","journal-title":"Mini. Rev. Org. Chem."},{"key":"80722_CR6","doi-asserted-by":"publisher","DOI":"10.1002\/9781118274408","volume-title":"Drug Repositioning: Bringing New Life to Shelved Assets and Existing Drugs","author":"MJ Barratt","year":"2012","unstructured":"Barratt, M. J. & Frail, D. Drug Repositioning: Bringing New Life to Shelved Assets and Existing Drugs (Wiley, New York, 2012)."},{"key":"80722_CR7","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1517\/17460441.2016.1154037","volume":"11","author":"BK Verlinden","year":"2016","unstructured":"Verlinden, B. K., Louw, A. & Birkholtz, L.-M. Resisting resistance: is there a solution for malaria?. Expert Opin. Drug Discov. 11, 395\u2013406 (2016).","journal-title":"Expert Opin. Drug Discov."},{"key":"80722_CR8","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/nrd1468","volume":"3","author":"TT Ashburn","year":"2004","unstructured":"Ashburn, T. T. & Thor, K. B. Drug repositioning: identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov. 3, 673\u2013683 (2004).","journal-title":"Nat. Rev. Drug Discov."},{"key":"80722_CR9","first-page":"1495","volume":"23","author":"A Kumar","year":"2016","unstructured":"Kumar, A., Naguib, Y. W., Shi, Y. C. & Cui, Z. A method to improve the efficacy of topical eflornithine hydrochloride cream. Drug Deliv. 23, 1495\u20131501 (2016).","journal-title":"Drug Deliv."},{"key":"80722_CR10","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/gm326","volume":"4","author":"YY Li","year":"2012","unstructured":"Li, Y. Y. & Jones, S. J. M. Drug repositioning for personalized medicine. Genome Med. 4, 27 (2012).","journal-title":"Genome Med."},{"key":"80722_CR11","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1007\/s10822-016-9946-8","volume":"30","author":"S Gathiaka","year":"2016","unstructured":"Gathiaka, S. et al. D3R grand challenge 2015: Evaluation of protein-ligand pose and affinity predictions. J. Comput. Aided. Mol. Des. 30, 651\u2013668 (2016).","journal-title":"J. Comput. Aided. Mol. Des."},{"key":"80722_CR12","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1021\/ci500081m","volume":"54","author":"Y Li","year":"2014","unstructured":"Li, Y., Han, L., Liu, Z. & Wang, R. Comparative assessment of scoring functions on an updated benchmark: 2. Evaluation methods and general results. J. Chem. Inf. Model. 54, 1717\u20131736 (2014).","journal-title":"J. Chem. Inf. Model."},{"key":"80722_CR13","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1002\/pro.3330","volume":"27","author":"CJ Williams","year":"2018","unstructured":"Williams, C. J. et al. MolProbity: More and better reference data for improved all-atom structure validation. Protein Sci. 27, 293\u2013315 (2018).","journal-title":"Protein Sci."},{"key":"80722_CR14","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1002\/prot.20801","volume":"62","author":"MA Robien","year":"2005","unstructured":"Robien, M. A. et al. Crystal structure of glyceraldehyde-3-phosphate dehydrogenase from Plasmodium falciparum at 2.25 \u00c5 resolution reveals intriguing extra electron density in the active site. Proteins Struct. Funct. Bioinf. 62, 570\u2013577 (2005).","journal-title":"Proteins Struct. Funct. Bioinf."},{"key":"80722_CR15","doi-asserted-by":"publisher","first-page":"8425","DOI":"10.1074\/jbc.REV120.009309","volume":"295","author":"AS Nasamu","year":"2020","unstructured":"Nasamu, A. S., Polino, A. J., Istvan, E. S. & Goldberg, D. E. Malaria parasite plasmepsins: More than just plain old degradative pepsins. J. Biol. Chem. 295, 8425\u20138441 (2020).","journal-title":"J. Biol. Chem."},{"key":"80722_CR16","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1021\/acs.jcim.7b00048","volume":"57","author":"J Ash","year":"2017","unstructured":"Ash, J. & Fourches, D. Characterizing the chemical space of ERK2 kinase inhibitors using descriptors computed from molecular dynamics trajectories. J. Chem. Inf. Model. 57, 1286\u20131299 (2017).","journal-title":"J. Chem. Inf. Model."},{"key":"80722_CR17","doi-asserted-by":"publisher","first-page":"5225","DOI":"10.1021\/bi3017075","volume":"52","author":"JC Oliver","year":"2013","unstructured":"Oliver, J. C., Linger, R. S., Chittur, S. V. & Davisson, V. J. Substrate activation and conformational dynamics of guanosine 5\u2032-monophosphate synthetase. Biochemistry 52, 5225\u20135235 (2013).","journal-title":"Biochemistry"},{"key":"80722_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncomms9930","volume":"6","author":"L Ballut","year":"2015","unstructured":"Ballut, L. et al. Active site coupling in Plasmodium falciparum GMP synthetase is triggered by domain rotation. Nat. Commun. 6, 1\u201313 (2015).","journal-title":"Nat. Commun."},{"key":"80722_CR19","doi-asserted-by":"publisher","first-page":"15451","DOI":"10.1038\/s41598-017-15571-7","volume":"7","author":"NM Hassan","year":"2017","unstructured":"Hassan, N. M., Alhossary, A. A., Mu, Y. & Kwoh, C. K. Protein-ligand blind docking using QuickVina-W with inter-process spatio-temporal integration. Sci. Rep. 7, 15451 (2017).","journal-title":"Sci. Rep."},{"key":"80722_CR20","first-page":"23","volume":"7","author":"S Shityakov","year":"2014","unstructured":"Shityakov, S. & F\u00f6rster, C. In silico predictive model to determine vector-mediated transport properties for the blood-brain barrier choline transporter. Adv. Appl. Bioinf. Chem. 7, 23\u201336 (2014).","journal-title":"Adv. Appl. Bioinf. Chem."},{"key":"80722_CR21","first-page":"D1074","volume":"46","author":"EJ Lo","year":"2017","unstructured":"Lo, E. J. et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 46, D1074\u2013D1082 (2017).","journal-title":"Nucleic Acids Res."},{"key":"80722_CR22","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott, O. & Olson, A. J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455\u2013461 (2010).","journal-title":"J. Comput. Chem."},{"key":"80722_CR23","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.drudis.2018.01.010","volume":"23","author":"S Mignani","year":"2018","unstructured":"Mignani, S. et al. Present drug-likeness filters in medicinal chemistry during the hit and lead optimization process: how far can they be simplified?. Drug Discov. Today 23, 605\u2013615 (2018).","journal-title":"Drug Discov. Today"},{"key":"80722_CR24","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.compbiolchem.2016.12.007","volume":"67","author":"M Kumar","year":"2017","unstructured":"Kumar, M., Kaur, T. & Sharma, A. Role of computational efficiency indices and pose clustering in effective decision making: an example of annulated furanones in Pf-DHFR space. Comput. Biol. Chem. 67, 48\u201361 (2017).","journal-title":"Comput. Biol. Chem."},{"key":"80722_CR25","doi-asserted-by":"publisher","first-page":"D930","DOI":"10.1093\/nar\/gky1075","volume":"47","author":"D Mendez","year":"2019","unstructured":"Mendez, D. et al. ChEMBL: towards direct deposition of bioassay data. Nucleic Acids Res. 47, D930\u2013D940 (2019).","journal-title":"Nucleic Acids Res."},{"key":"80722_CR26","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1021\/ci300566n","volume":"53","author":"J Desaphy","year":"2013","unstructured":"Desaphy, J., Raimbaud, E., Ducrot, P. & Rognan, D. Encoding protein-ligand interaction patterns in fingerprints and graphs. J. Chem. Inf. Model. 53, 623\u2013637 (2013).","journal-title":"J. Chem. Inf. Model."},{"key":"80722_CR27","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1002\/cmdc.200600223","volume":"1","author":"C Boss","year":"2006","unstructured":"Boss, C. et al. Achiral, cheap, and potent inhibitors of plasmepsins I, II, and IV. ChemMedChem 1, 1341\u20131345 (2006).","journal-title":"ChemMedChem"},{"key":"80722_CR28","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1016\/j.jmb.2006.07.067","volume":"362","author":"E Barratt","year":"2006","unstructured":"Barratt, E. et al. Thermodynamic penalty arising from burial of a ligand polar group within a hydrophobic pocket of a protein receptor. J. Mol. Biol. 362, 994\u20131003 (2006).","journal-title":"J. Mol. Biol."},{"key":"80722_CR29","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1002\/cmdc.200900078","volume":"4","author":"R Friedman","year":"2009","unstructured":"Friedman, R. & Caflisch, A. Discovery of plasmepsin inhibitors by fragment-based docking and consensus scoring. ChemMedChem 4, 1317\u20131326 (2009).","journal-title":"ChemMedChem"},{"key":"80722_CR30","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.str.2007.11.014","volume":"16","author":"A Merckx","year":"2008","unstructured":"Merckx, A. et al. Structures of P. falciparum protein kinase 7 identify an activation motif and leads for inhibitor design. Structure 16, 228\u2013238 (2008).","journal-title":"Structure"},{"key":"80722_CR31","doi-asserted-by":"publisher","first-page":"8061","DOI":"10.1021\/acs.jmedchem.8b00329","volume":"61","author":"DG Cabrera","year":"2018","unstructured":"Cabrera, D. G. et al. Plasmodial kinase inhibitors: license to cure?. J. Med. Chem. 61, 8061\u20138077 (2018).","journal-title":"J. Med. Chem."},{"key":"80722_CR32","doi-asserted-by":"publisher","first-page":"3446","DOI":"10.1016\/j.jmb.2013.06.037","volume":"425","author":"K Fritz-Wolf","year":"2013","unstructured":"Fritz-Wolf, K. et al. Crystal structure of the Plasmodium falciparum thioredoxin reductase-thioredoxin complex. J. Mol. Biol. 425, 3446\u20133460 (2013).","journal-title":"J. Mol. Biol."},{"key":"80722_CR33","doi-asserted-by":"publisher","first-page":"8511","DOI":"10.1073\/pnas.1118370109","volume":"109","author":"ER Derbyshire","year":"2012","unstructured":"Derbyshire, E. R., Prud\u00eancio, M., Mota, M. M. & Clardy, J. Liver-stage malaria parasites vulnerable to diverse chemical scaffolds. Proc. Natl. Acad. Sci. USA 109, 8511\u20138516 (2012).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"80722_CR34","doi-asserted-by":"publisher","first-page":"D1102","DOI":"10.1093\/nar\/gky1033","volume":"47","author":"S Kim","year":"2019","unstructured":"Kim, S. et al. PubChem 2019 update: improved access to chemical data. Nucleic Acids Res. 47, D1102\u2013D1109 (2019).","journal-title":"Nucleic Acids Res."},{"key":"80722_CR35","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/S0166-6851(97)00052-2","volume":"87","author":"PM F\u00e4rber","year":"1997","unstructured":"F\u00e4rber, P. M., Graeser, R., Franklin, R. M. & Kappes, B. Molecular cloning and characterization of a second calcium-dependent protein kinase of Plasmodium falciparum. Mol. Biochem. Parasitol. 87, 211\u2013216 (1997).","journal-title":"Mol. Biochem. Parasitol."},{"key":"80722_CR36","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1134\/S0026893308040195","volume":"42","author":"MY Lobanov","year":"2008","unstructured":"Lobanov, M. Y., Bogatyreva, N. S. & Galzitskaya, O. V. Radius of gyration as an indicator of protein structure compactness. Mol. Biol. 42, 623\u2013628 (2008).","journal-title":"Mol. Biol."},{"key":"80722_CR37","doi-asserted-by":"publisher","first-page":"e1000634","DOI":"10.1371\/journal.pcbi.1000634","volume":"6","author":"D Seeliger","year":"2010","unstructured":"Seeliger, D. & De Groot, B. L. Conformational transitions upon ligand binding: Holo-structure prediction from apo conformations. PLoS Comput. Biol. 6, e1000634 (2010).","journal-title":"PLoS Comput. Biol."},{"key":"80722_CR38","unstructured":"Donev, R. Personalized Medicine, Volume 102 - 1st Edition."},{"key":"80722_CR39","doi-asserted-by":"publisher","unstructured":"Maiorov, V. N. & Crippen, G. M. Size\u2010independent comparison of protein three\u2010dimensional structures. Proteins: Structure, Function, and Bioinformatics vol. 22. https:\/\/doi.org\/10.1002\/prot.340220308 (1995).","DOI":"10.1002\/prot.340220308"},{"key":"80722_CR40","doi-asserted-by":"publisher","first-page":"53","DOI":"10.33011\/livecoms.1.1.5068","volume":"1","author":"J Lemkul","year":"2019","unstructured":"Lemkul, J. From proteins to perturbed hamiltonians: a suite of tutorials for the GROMACS-2018 molecular simulation package [Article v1.0]. Living J. Comput. Mol. Sci. 1, 53 (2019).","journal-title":"Living J. Comput. Mol. Sci."},{"key":"80722_CR41","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1038\/nrd2445","volume":"6","author":"PD Leeson","year":"2007","unstructured":"Leeson, P. D. & Springthorpe, B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat. Rev. Drug Discov. 6, 881\u2013890 (2007).","journal-title":"Nat. Rev. Drug Discov."},{"key":"80722_CR42","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1517\/17460441.2.4.469","volume":"2","author":"C Abad-Zapatero","year":"2007","unstructured":"Abad-Zapatero, C. Ligand efficiency indices for effective drug discovery. Expert Opin. Drug Discov. 2, 469\u2013488 (2007).","journal-title":"Expert Opin. Drug Discov."},{"key":"80722_CR43","doi-asserted-by":"publisher","first-page":"113","DOI":"10.4155\/fmc.12.208","volume":"5","author":"KD Freeman-Cook","year":"2013","unstructured":"Freeman-Cook, K. D., Hoffman, R. L. & Johnson, T. W. Lipophilic efficiency: the most important efficiency metric in medicinal chemistry. Future Med. Chem. 5, 113\u2013115 (2013).","journal-title":"Future Med. Chem."},{"key":"80722_CR44","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1007\/s10822-016-9930-3","volume":"30","author":"I Slynko","year":"2016","unstructured":"Slynko, I., Da Silva, F., Bret, G. & Rognan, D. Docking pose selection by interaction pattern graph similarity: application to the D3R grand challenge 2015. J. Comput. Aided. Mol. Des. 30, 669\u2013683 (2016).","journal-title":"J. Comput. Aided. Mol. Des."},{"key":"80722_CR45","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1126\/science.781840","volume":"193","author":"W Trager","year":"1976","unstructured":"Trager, W. et al. Human malaria parasites in continuous culture. Science (80-) 193, 673\u2013675 (1976).","journal-title":"Science (80-)"},{"key":"80722_CR46","doi-asserted-by":"publisher","first-page":"9059","DOI":"10.1073\/pnas.0802982105","volume":"105","author":"D Plouffe","year":"2008","unstructured":"Plouffe, D. et al. In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen. Proc. Natl. Acad. Sci. USA 105, 9059\u20139064 (2008).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"80722_CR47","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.1016\/j.bmc.2010.01.068","volume":"18","author":"FJ Prado-Prado","year":"2010","unstructured":"Prado-Prado, F. J., Garc\u00eda-Mera, X. & Gonz\u00e1lez-D\u00edaz, H. Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species. Bioorg. Med. Chem. 18, 2225\u20132231 (2010).","journal-title":"Bioorg. Med. Chem."},{"key":"80722_CR48","unstructured":"Brody, T. Clinical Trials 2nd edition. https:\/\/www.elsevier.com\/books\/clinical-trials\/brody\/978-0-12-804217-5 (2016)."},{"key":"80722_CR49","unstructured":"Fingolimod in COVID-19 - Full Text View - ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04280588."},{"key":"80722_CR50","doi-asserted-by":"publisher","first-page":"e1002139","DOI":"10.1371\/journal.pcbi.1002139","volume":"7","author":"YY Li","year":"2011","unstructured":"Li, Y. Y., An, J. & Jones, S. J. M. A computational approach to finding novel targets for existing drugs. PLoS Comput. Biol. 7, e1002139 (2011).","journal-title":"PLoS Comput. Biol."},{"key":"80722_CR51","doi-asserted-by":"publisher","first-page":"6560","DOI":"10.1021\/jm301916b","volume":"56","author":"T Zhu","year":"2013","unstructured":"Zhu, T. et al. Hit identification and optimization in virtual screening: practical recommendations based upon a critical literature analysis. J. Med. Chem. 56, 6560\u20136572 (2013).","journal-title":"J. Med. Chem."},{"key":"80722_CR52","doi-asserted-by":"publisher","first-page":"D399","DOI":"10.1093\/nar\/gku928","volume":"43","author":"J Desaphy","year":"2015","unstructured":"Desaphy, J., Bret, G., Rognan, D. & Kellenberger, E. Sc-PDB: A 3D-database of ligandable binding sites-10 years on. Nucleic Acids Res. 43, D399\u2013D404 (2015).","journal-title":"Nucleic Acids Res."},{"key":"80722_CR53","unstructured":"Huey, R. & Morris, G. M. Using AutoDock with AutoDockTools: A Tutorial. http:\/\/mgltools.scripps.edu\/downloads\/previous-releases\/downloads\/tars\/releases\/DocTars\/DOCPACKS\/AutoDockTools\/doc\/UsingAutoDockWithADT.pdf."},{"key":"80722_CR54","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/nchem.1243","volume":"4","author":"GR Bickerton","year":"2012","unstructured":"Bickerton, G. R., Paolini, G. V., Besnard, J., Muresan, S. & Hopkins, A. L. Quantifying the chemical beauty of drugs. Nat. Chem. 4, 90\u201398 (2012).","journal-title":"Nat. Chem."},{"key":"80722_CR55","unstructured":"Landrum, G. RDKit: open-source cheminformatics software. (2016)."},{"key":"80722_CR56","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1021\/ci990307l","volume":"39","author":"SA Wildman","year":"1999","unstructured":"Wildman, S. A. & Crippen, G. M. Prediction of physicochemical parameters by atomic contributions. J. Chem. Inf. Comput. Sci. 39, 868\u2013873 (1999).","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"80722_CR57","doi-asserted-by":"crossref","unstructured":"Trott, O. & Olson, A. J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, NA-NA (2009).","DOI":"10.1002\/jcc.21334"},{"key":"80722_CR58","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/minf.201400132","volume":"34","author":"H Li","year":"2015","unstructured":"Li, H., Leung, K.-S., Wong, M.-H. & Ballester, P. J. Improving AutoDock vina using random forest: the growing accuracy of binding affinity prediction by the effective exploitation of larger data sets. Mol. Inform. 34, 115\u2013126 (2015).","journal-title":"Mol. Inform."},{"key":"80722_CR59","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1007\/s10822-016-9900-9","volume":"30","author":"MM Jaghoori","year":"2016","unstructured":"Jaghoori, M. M., Bleijlevens, B. & Olabarriaga, S. D. 1001 Ways to run AutoDock Vina for virtual screening. J. Comput. Aided. Mol. Des. 30, 237\u2013249 (2016).","journal-title":"J. Comput. Aided. Mol. Des."},{"key":"80722_CR60","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1590\/S0103-50532013000300015","volume":"24","author":"RS Affonso","year":"2013","unstructured":"Affonso, R. S., Guimar\u00e3es, A. P., Oliveira, A. A., Slana, G. B. C. & Fran\u00e7a, T. C. C. Applications of molecular modeling in the design of new insect repellents targeting the odorant binding protein of anopheles gambiae. J. Braz. Chem. Soc. 24, 473\u2013482 (2013).","journal-title":"J. Braz. Chem. Soc."},{"key":"80722_CR61","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","volume":"1\u20132","author":"MJ Abraham","year":"2015","unstructured":"Abraham, M. J. et al. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1\u20132, 19\u201325 (2015).","journal-title":"SoftwareX"},{"key":"80722_CR62","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s10822-012-9626-2","volume":"27","author":"N Schneider","year":"2013","unstructured":"Schneider, N., Lange, G., Hindle, S., Klein, R. & Rarey, M. A consistent description of HYdrogen bond and DEhydration energies in protein\u2013ligand complexes: methods behind the HYDE scoring function. J. Comput. Aided. Mol. Des. 27, 15\u201329 (2013).","journal-title":"J. Comput. Aided. Mol. Des."},{"key":"80722_CR63","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s10822-017-0046-1","volume":"32","author":"P Da Silva Figueiredo Celestino Gomes","year":"2018","unstructured":"Da Silva Figueiredo Celestino Gomes, P., Da Silva, F., Bret, G. & Rognan, D. Ranking docking poses by graph matching of protein\u2013ligand interactions: lessons learned from the D3R Grand Challenge 2. J. Comput. Aided. Mol. Des. 32, 75\u201387 (2018).","journal-title":"J. Comput. Aided. Mol. Des."},{"key":"80722_CR64","doi-asserted-by":"publisher","first-page":"e0171433","DOI":"10.1371\/journal.pone.0171433","volume":"12","author":"Q Luo","year":"2017","unstructured":"Luo, Q. et al. The scoring bias in reverse docking and the score normalization strategy to improve success rate of target fishing. PLoS ONE 12, e0171433 (2017).","journal-title":"PLoS ONE"},{"key":"80722_CR65","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1021\/jm030161o","volume":"47","author":"GPA Vigers","year":"2004","unstructured":"Vigers, G. P. A. & Rizzi, J. P. Multiple active site corrections for docking and virtual screening. J. Med. Chem. 47, 80\u201389 (2004).","journal-title":"J. Med. Chem."},{"key":"80722_CR66","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1021\/ci050407t","volume":"46","author":"M Jacobsson","year":"2006","unstructured":"Jacobsson, M. & Karl\u00e9n, A. Ligand bias of scoring functions in structure-based virtual screening. J. Chem. Inf. Model. 46, 1334\u20131343 (2006).","journal-title":"J. Chem. Inf. Model."},{"key":"80722_CR67","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1021\/ci060152z","volume":"46","author":"Y Fukunishi","year":"2006","unstructured":"Fukunishi, Y., Kubota, S. & Nakamura, H. Noise reduction method for molecular interaction energy: application to in silico drug screening and in silico target protein screening. J. Chem. Inf. Model. 46, 2071\u20132084 (2006).","journal-title":"J. Chem. Inf. Model."},{"key":"80722_CR68","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","volume":"17","author":"P Virtanen","year":"2020","unstructured":"Virtanen, P. et al. SciPy 1.0: fundamental algorithms for scientific computing in Python. Nat. Methods 17, 261\u2013272 (2020).","journal-title":"Nat. Methods"},{"key":"80722_CR69","unstructured":"Arnott, J. A., Kumar, R. & Planey, S. L. Lipophilicity indices for drug development. J. Appl. Biopharm. Pharmacokinet. (2013)."},{"key":"80722_CR70","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1002\/prot.10613","volume":"55","author":"MP Jacobson","year":"2004","unstructured":"Jacobson, M. P. et al. A hierarchical approach to all-atom protein loop prediction. Proteins Struct. Funct. Genet. 55, 351\u2013367 (2004).","journal-title":"Proteins Struct. Funct. Genet."},{"key":"80722_CR71","doi-asserted-by":"publisher","first-page":"2824","DOI":"10.1021\/acssynbio.8b00219","volume":"7","author":"G Pines","year":"2018","unstructured":"Pines, G. et al. Genomic deoxyxylulose phosphate reductoisomerase (DXR) mutations conferring resistance to the antimalarial drug fosmidomycin in E. coli. ACS Synth. Biol. 7, 2824\u20132832 (2018).","journal-title":"ACS Synth. Biol."},{"key":"80722_CR72","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1021\/ct5010406","volume":"11","author":"CW Hopkins","year":"2015","unstructured":"Hopkins, C. W., Le Grand, S., Walker, R. C. & Roitberg, A. E. Long-time-step molecular dynamics through hydrogen mass repartitioning. J. Chem. Theory Comput. 11, 1864\u20131874 (2015).","journal-title":"J. Chem. Theory Comput."},{"key":"80722_CR73","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.jmgm.2013.05.004","volume":"44","author":"K Mal\u00e1\u010d","year":"2013","unstructured":"Mal\u00e1\u010d, K. & Barv\u00edk, I. Complex between Human RNase HI and the phosphonate-DNA\/RNA duplex: Molecular dynamics study. J. Mol. Graph. Model. 44, 81\u201390 (2013).","journal-title":"J. Mol. Graph. Model."},{"key":"80722_CR74","doi-asserted-by":"publisher","first-page":"E7311","DOI":"10.1073\/pnas.1707547114","volume":"114","author":"S Gu","year":"2017","unstructured":"Gu, S. et al. Phosphoantigen-induced conformational change of butyrophilin 3A1 (BTN3A1) and its implication on V\u03b39V\u03b42 T cell activation. Proc. Natl. Acad. Sci. USA 114, E7311\u2013E7320 (2017).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"80722_CR75","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1186\/1756-0500-5-367","volume":"5","author":"AW Sousa da Silva","year":"2012","unstructured":"Sousa da Silva, A. W. & Vranken, W. F. ACPYPE\u2014AnteChamber PYthon Parser interfacE. BMC Res. Notes 5, 367 (2012).","journal-title":"BMC Res. Notes"},{"key":"80722_CR76","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1093\/bioinformatics\/btt055","volume":"29","author":"S Pronk","year":"2013","unstructured":"Pronk, S. et al. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics 29, 845\u2013854 (2013).","journal-title":"Bioinformatics"},{"key":"80722_CR77","doi-asserted-by":"publisher","first-page":"1950","DOI":"10.1002\/prot.22711","volume":"78","author":"K Lindorff-Larsen","year":"2010","unstructured":"Lindorff-Larsen, K. et al. Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins 78, 1950\u20131958 (2010).","journal-title":"Proteins"},{"key":"80722_CR78","unstructured":"Kluyver, T. et al. Jupyter Notebooks-a publishing format for reproducible computational workflows. in ELPUB 87\u201390 (2016)."},{"key":"80722_CR79","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1093\/bioinformatics\/btx789","volume":"34","author":"H Nguyen","year":"2018","unstructured":"Nguyen, H., Case, D. A. & Rose, A. S. NGLview\u2013interactive molecular graphics for Jupyter notebooks. Bioinformatics 34, 1241\u20131242 (2018).","journal-title":"Bioinformatics"},{"key":"80722_CR80","volume-title":"PYTRAJ: Interactive Data Analysis for Molecular Dynamics Simulations","author":"H Nguyen","year":"2016","unstructured":"Nguyen, H., Roe, D. R., Swails, J. & Case, D. A. PYTRAJ: Interactive Data Analysis for Molecular Dynamics Simulations (NJ Rutgers Univ, New Brunswick, 2016)."},{"key":"80722_CR81","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1002\/cmdc.201800235","volume":"13","author":"MJ Lunga","year":"2018","unstructured":"Lunga, M. J. et al. Expanding the SAR of nontoxic antiplasmodial indolyl-3-ethanone ethers and thioethers. ChemMedChem 13, 1353\u20131362 (2018).","journal-title":"ChemMedChem"},{"key":"80722_CR82","doi-asserted-by":"publisher","first-page":"205","DOI":"10.4269\/ajtmh.1993.48.205","volume":"48","author":"MT Makler","year":"1993","unstructured":"Makler, M. T. & Hinrichs, D. J. Measurement of the lactate dehydrogenase activity of Plasmodium falciparum as an assessment of parasitemia. Am. J. Trop. Med. Hyg. 48, 205\u2013210 (1993).","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"80722_CR83","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1590\/S1806-83242009000300006","volume":"23","author":"RC Borra","year":"2009","unstructured":"Borra, R. C., Lotufo, M. A., Gagioti, S. M., Barros, F. M. & Andrade, P. M. A simple method to measure cell viability in proliferation and cytotoxicity assays. Braz. Oral Res. 23, 255\u2013262 (2009).","journal-title":"Braz. Oral Res."},{"key":"80722_CR84","unstructured":"Riss, T. L. et al. Cell viability assays. in Assay Guidance Manual [Internet] (Eli Lilly & Company and the National Center for Advancing Translational Sciences, 2016)."},{"key":"80722_CR85","unstructured":"seaborn: statistical data visualization \u2014 seaborn 0.11.0 documentation. https:\/\/seaborn.pydata.org\/."},{"key":"80722_CR86","doi-asserted-by":"publisher","first-page":"D668","DOI":"10.1093\/nar\/gkj067","volume":"34","author":"DS Wishart","year":"2005","unstructured":"Wishart, D. S. DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 34, D668\u2013D672 (2005).","journal-title":"Nucleic Acids Res."},{"key":"80722_CR87","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1758-2946-3-33","volume":"3","author":"NM O\u2019Boyle","year":"2011","unstructured":"O\u2019Boyle, N. M. et al. Open Babel: an open chemical toolbox. J. Cheminform. 3, 33 (2011).","journal-title":"J. Cheminform."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80722-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80722-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80722-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T13:31:40Z","timestamp":1697549500000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-80722-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,14]]},"references-count":87,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["80722"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-80722-2","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.739373307.793587535","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,14]]},"assertion":[{"value":"21 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1413"}}