{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:24:25Z","timestamp":1791915865460,"version":"4.3.4"},"reference-count":71,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"New strategic research project (P2P) fiscal year 2022, Walailak University, Thailand","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Acanthamoeba species are capable of causing amoebic keratitis (AK). As a monotherapy, alpha-mangostin is effective for the treatment of AK; however, its bioavailability is quite poor. Moreover, the efficacy of therapy is contingent on the parasite and virulent strains. To improve readiness against AK, it is necessary to find other derivatives with accurate target identification. Beta-tubulin (BT) has been used as a target for anti-Acanthamoeba (A. keratitis). In this work, therefore, a model of the BT protein of A. keratitis was constructed by homology modeling utilizing the amino acid sequence from NCBI (GenBank: JQ417907.1). Ramachandran Plot was responsible for validating the protein PDB. The verified BT PDB was used for docking with the specified ligand. Based on an improved docking score compared to alpha-mangostin (AM), two modified compounds were identified: 1,6-dihydroxy-7-methoxy-2,8-bis(3-methylbut-2-en-1-yl)-9H-xanthen-9-one (C1) and 1,6-dihydroxy-2,8-bis(3-methylbut-2-en-1-yl)-9H-xanthen-9-one (C2). In addition, molecular dynamics simulations were conducted to analyze the interaction characteristics of the two bound BT\u2013new compound complexes. During simulations, the TRP9, ARG50, VAL52, and GLN122 residues of BT-C1 that align to the identical residues in BT-AM generate consistent hydrogen bond interactions with 0\u20133 and 0\u20132. However, the BT-C2 complex has a different binding site, TYR 258, ILE 281, and SER 302, and can form more hydrogen bonds in the range 0\u20134. Therefore, this study reveals that C1 and C2 inhibit BT as an additive or synergistic effect; however, further in vitro and in vivo studies are needed.<\/jats:p>","DOI":"10.3390\/molecules27196338","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T03:30:37Z","timestamp":1664335837000},"page":"6338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["Homology Modeling, Molecular Docking, Molecular Dynamic Simulation, and Drug-Likeness of the Modified Alpha-Mangostin against the \u03b2-Tubulin Protein of Acanthamoeba Keratitis"],"prefix":"10.3390","volume":"27","author":[{"given":"Tassanee","family":"Ongtanasup","sequence":"first","affiliation":[{"name":"Department of Applied Thai Traditional Medicine, School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anisha","family":"Mazumder","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Charles University, 50005 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupma","family":"Dwivedi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Charles University, 50005 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0577-6225","authenticated-orcid":false,"given":"Komgrit","family":"Eawsakul","sequence":"additional","affiliation":[{"name":"Department of Applied Thai Traditional Medicine, School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.26444\/aaem\/99683","article-title":"Effect of povidone iodine, chlorhexidine digluconate and toyocamycin on amphizoic amoebic strains, infectious agents of Acanthamoeba keratitis\u2013a growing threat to human health worldwide","volume":"25","author":"Padzik","year":"2018","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/j.1574-6976.2006.00023.x","article-title":"Acanthamoeba: Biology and increasing importance in human health","volume":"30","author":"Khan","year":"2006","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_3","first-page":"893","article-title":"A Review of the Current Research Trends in the Application of Medicinal Plants as a Source for Novel Therapeutic Agents Against Acanthamoeba Infections","volume":"15","author":"Niyyati","year":"2016","journal-title":"Iran. J. Pharm. Res. IJPR"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6646","DOI":"10.1021\/jm8008508","article-title":"Semisynthetic Cyclopamine Analogues as Potent and Orally Bioavailable Hedgehog Pathway Antagonists","volume":"51","author":"Tremblay","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nature12051","article-title":"High-level semi-synthetic production of the potent antimalarial artemisinin","volume":"496","author":"Paddon","year":"2013","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1128\/AAC.00355-07","article-title":"Molecular Basis for Resistance of Acanthamoeba Tubulins to All Major Classes of Antitubulin Compounds","volume":"52","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1080\/20477724.2021.1985892","article-title":"Opportunistic free-living amoebal pathogens","volume":"116","author":"Mungroo","year":"2022","journal-title":"Pathog. Glob. Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1016\/0006-2952(84)90515-X","article-title":"A comparison of the interaction of anthelmintic benzimidazoles with tubulin isolated from mammalian tissue and the parasitic nematode Ascaridia galli","volume":"33","author":"Dawson","year":"1984","journal-title":"Biochem. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1242\/jcs.00869","article-title":"Maternally expressed and partially redundant \u03b2-tubulins in Caenorhabditis elegans are autoregulated","volume":"117","author":"Ellis","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.2174\/092986709787846488","article-title":"Tubulin: A target for antineoplastic drugs into the cancer cells but also in the peripheral nervous system","volume":"16","author":"Canta","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.molbiopara.2005.08.020","article-title":"Cellular and molecular actions of dinitroaniline and phosphorothioamidate herbicides on Plasmodium falciparum: Tubulin as a specific antimalarial target","volume":"145","author":"Fennell","year":"2006","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1089\/ars.2013.5595","article-title":"Antihelminthic Benzimidazoles Are Novel HIF Activators That Prevent Oxidative Neuronal Death via Binding to Tubulin","volume":"22","author":"Aleyasin","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1517\/13543776.2011.545349","article-title":"Microtubules as antifungal and antiparasitic drug targets","volume":"21","author":"Chatterji","year":"2011","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1128\/AAC.38.9.2086","article-title":"Antiprotozoal activities of benzimidazoles and correlations with beta-tubulin sequence","volume":"38","author":"Katiyar","year":"1994","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"974","DOI":"10.5958\/0974-360X.2020.00182.1","article-title":"A review on medicinal properties of mangosteen (Garcinia mangostana L.)","volume":"13","author":"Ansori","year":"2020","journal-title":"Res. J. Pharm. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yahia, E.M. (2011). 1\u2014Mangosteen (Garcinia mangostana L.). Postharvest Biology and Technology of Tropical and Subtropical Fruits, Woodhead Publishing.","DOI":"10.1533\/9780857092885"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1016\/j.fct.2008.07.024","article-title":"Medicinal properties of mangosteen (Garcinia mangostana)","volume":"46","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1002\/mnfr.201300771","article-title":"Dietary \u03b1-mangostin, a xanthone from mangosteen fruit, exacerbates experimental colitis and promotes dysbiosis in mice","volume":"58","author":"Galley","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_19","first-page":"844","article-title":"Mangosteen (Garcinia mangostana)","volume":"2011","author":"Cassileth","year":"2011","journal-title":"Oncology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1021\/jf052649z","article-title":"Antioxidant Xanthones from the Pericarp of Garcinia mangostana (Mangosteen)","volume":"54","author":"Jung","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.3390\/nu5083163","article-title":"Biological Activities and Bioavailability of Mangosteen Xanthones: A Critical Review of the Current Evidence","volume":"5","author":"Failla","year":"2013","journal-title":"Nutrients"},{"key":"ref_22","first-page":"253","article-title":"Antioxidant and anticancer potential of mangosteen fruit, Garcinia mangostana against hepatocellular carcinoma (HePG-2) cell line","volume":"5","author":"Manimekalai","year":"2016","journal-title":"World J. Pharm. Pharm. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1002\/ptr.2730","article-title":"Garcinia mangostana L.: A phytochemical and pharmacological review","volume":"23","author":"Obolskiy","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s11101-011-9207-3","article-title":"An overview on genus garcinia: Phytochemical and therapeutical aspects","volume":"10","author":"Hemshekhar","year":"2011","journal-title":"Phytochem. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1248\/bpb.25.1137","article-title":"Inhibitions of Histamine Release and Prostaglandin E2 Synthesis by Mangosteen, a Thai Medicinal Plant","volume":"25","author":"Nakatani","year":"2002","journal-title":"Biol. Pharm. Bull."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9645","DOI":"10.1007\/s00253-020-10914-3","article-title":"Metal coordination by L-amino acid oxidase derived from flounder Platichthys stellatus is structurally essential and regulates antibacterial activity","volume":"104","author":"Kasai","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.cell.2019.09.030","article-title":"Structure of the Decorated Ciliary Doublet Microtubule","volume":"179","author":"Ma","year":"2019","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1093\/bioinformatics\/btz828","article-title":"QMEANDisCo\u2014Distance constraints applied on model quality estimation","volume":"36","author":"Studer","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_29","first-page":"135","article-title":"Identification of novel antagonists of the ecdysone receptor from the desert locust (Schistocerca gregaria) by in silico modelling","volume":"44","author":"Hemmati","year":"2021","journal-title":"Plant Prot. (Sci. J. Agric.)"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.3390\/plants11141835","article-title":"The Cholesterol-Modulating Effect of the New Herbal Medicinal Recipe from Yellow Vine (Coscinium fenestratum (Goetgh.)), Ginger (Zingiber officinale Roscoe.), and Safflower (Carthamus tinctorius L.) on Suppressing PCSK9 Expression to Upregulate LDLR Expression in HepG2 Cells","volume":"11","author":"Ongtanasup","year":"2022","journal-title":"Plants"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"103389","DOI":"10.1016\/j.sjbs.2022.103389","article-title":"In silico investigation of ACE2 and the main protease of SARS-CoV-2 with phytochemicals from Myristica fragrans (Houtt.) for the discovery of a novel COVID-19 drug","volume":"29","author":"Ongtanasup","year":"2022","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e08078","DOI":"10.1016\/j.heliyon.2021.e08078","article-title":"Computational study and in vitro alpha-glucosidase inhibitory effects of medicinal plants from a Thai folk remedy","volume":"7","author":"Eawsakul","year":"2021","journal-title":"Heliyon"},{"key":"ref_33","first-page":"250","article-title":"Hard and Soft Acids and Bases, Dowden, Hutchinson and Ross","volume":"26","author":"Pearson","year":"1993","journal-title":"Inorg Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1021\/la950725u","article-title":"Correlation between Lewis Acid\u2212Base Surface Interaction Components and Linear Solvation Energy Relationship Solvatochromic \u03b1 and \u03b2 Parameters","volume":"12","author":"Lee","year":"1996","journal-title":"Langmuir"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1002\/ejoc.200500856","article-title":"Synthesis and Precursor-Directed Biosynthesis of New Hormaomycin Analogues","volume":"2006","author":"Zlatopolskiy","year":"2006","journal-title":"Eur. J. Org. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1007\/s11030-021-10295-3","article-title":"Recent trends in the chemistry of Sandmeyer reaction: A review","volume":"26","author":"Akhtar","year":"2022","journal-title":"Mol. Divers."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1021\/ol2000556","article-title":"Efficient Monophosphorus Ligands for Palladium-Catalyzed Miyaura Borylation","volume":"13","author":"Tang","year":"2011","journal-title":"Org. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.1039\/C5OB00170F","article-title":"Development of a flow method for the hydroboration\/oxidation of olefins","volume":"13","author":"Souto","year":"2015","journal-title":"Org. Biomol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1046\/j.1462-5822.2001.00116.x","article-title":"Cellular mechanisms of microbial proteins contributing to invasion of the blood\u2013brain barrier","volume":"3","author":"Huang","year":"2001","journal-title":"Cell. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"259","DOI":"10.2165\/11597530-000000000-00000","article-title":"Blood-Brain Barrier Permeation and Efflux Exclusion of Anticholinergics Used in the Treatment of Overactive Bladder","volume":"29","author":"Chancellor","year":"2012","journal-title":"Drugs Aging"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1081\/DMR-120001389","article-title":"Drugs as P-glycoprotein substrates, inhibitors, and inducers","volume":"34","author":"Kim","year":"2002","journal-title":"Drug Metab. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ijpharm.2005.05.034","article-title":"A combined cell based approach to identify P-glycoprotein substrates and inhibitors in a single assay","volume":"301","author":"Balimane","year":"2005","journal-title":"Int. J. Pharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1002\/cbdv.200690111","article-title":"The Biochemistry of Drug Metabolism\u2014An Introduction","volume":"3","author":"Testa","year":"2006","journal-title":"Chem. Biodivers."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1081\/DMR-120001387","article-title":"Characteristics and common properties of inhibitors, inducers, and activators of CYP enzymes","volume":"34","author":"Hollenberg","year":"2002","journal-title":"Drug Metab. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nrd4581","article-title":"Predicting drug metabolism: Experiment and\/or computation?","volume":"14","author":"Kirchmair","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1177\/0091270007312153","article-title":"New Era in Drug Interaction Evaluation: US Food and Drug Administration Update on CYP Enzymes, Transporters, and the Guidance Process","volume":"48","author":"Huang","year":"2008","journal-title":"J. Clin. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1021\/jm020017n","article-title":"Molecular Properties That Influence the Oral Bioavailability of Drug Candidates","volume":"45","author":"Veber","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3867","DOI":"10.1021\/jm000292e","article-title":"Prediction of Drug Absorption Using Multivariate Statistics","volume":"43","author":"Egan","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6441","DOI":"10.1128\/AAC.00686-16","article-title":"The Development of Drugs against Acanthamoeba Infections","volume":"60","author":"Siddiqui","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1093\/nar\/gkg520","article-title":"SWISS-MODEL: An automated protein homology-modeling server","volume":"31","author":"Schwede","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"W510","DOI":"10.1093\/nar\/gkp322","article-title":"QMEAN server for protein model quality estimation","volume":"37","author":"Benkert","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/bib\/2.2.195","article-title":"Swiss-PDB Viewer (Deep View)","volume":"2","author":"Kaplan","year":"2001","journal-title":"Brief. Bioinform."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/prot.22879","article-title":"Automated minimization of steric clashes in protein structures","volume":"79","author":"Ramachandran","year":"2011","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1093\/bioinformatics\/btr374","article-title":"Gaia: Automated quality assessment of protein structure models","volume":"27","author":"Kota","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"100216","DOI":"10.1016\/j.imu.2019.100216","article-title":"Structure based in-silico study on UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-2,6-diaminopimelate ligase (MurE) from Acinetobacter baumannii as a drug target against nosocomial infections","volume":"16","author":"Amera","year":"2019","journal-title":"Inform. Med. Unlocked"},{"key":"ref_58","unstructured":"Laskowski, R., MacArthur, M., and Thornton, J. (2006). PROCHECK: Validation of protein-structure coordinates. Int. Tables Crystallogr., in press."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"W374","DOI":"10.1093\/nar\/gky380","article-title":"CavityPlus: A web server for protein cavity detection with pharmacophore modelling, allosteric site identification and covalent ligand binding ability prediction","volume":"46","author":"Xu","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"D1388","DOI":"10.1093\/nar\/gkaa971","article-title":"PubChem in 2021: New data content and improved web interfaces","volume":"49","author":"Kim","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1758-2946-4-17","article-title":"Avogadro: An advanced semantic chemical editor, visualization, and analysis platform","volume":"4","author":"Hanwell","year":"2012","journal-title":"J. Cheminform."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1273\/cbij.9.52","article-title":"Validation of ArgusLab Efficiencies for Binding Free Energy Calculations","volume":"9","author":"Oda","year":"2009","journal-title":"Chem-Bio Inform. J."},{"key":"ref_63","unstructured":"Morris, G.M., Goodsell, D.S., Huey, R., Hart, W.E., Halliday, S., Belew, R., and Olson, A.J. (2001). AutoDock. Automated Docking of Flexible Ligands to Receptor-User Guide, The Scripps Research Institute, Molecular Graphics Laboratory, Department of Molecular Biology."},{"key":"ref_64","unstructured":"Biovia, D.S. (2017). Discovery Studio Visualizer, BIOVIA."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"14303","DOI":"10.1021\/ie3023675","article-title":"COSMOquick: A Novel Interface for Fast \u03c3-Profile Composition and Its Application to COSMO-RS Solvent Screening Using Multiple Reference Solvents","volume":"51","author":"Loschen","year":"2012","journal-title":"Ind. Eng. Chem. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.bbrc.2022.07.090","article-title":"Structural insight into substrate binding of Acinetobacter baumannii polyphosphate-AMP phosphotransferase (PPK2), a novel drug target","volume":"626","author":"Gautam","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_67","unstructured":"Bekker, H., Berendsen, H., Dijkstra, E., Achterop, S., Vondrumen, R., VANDERSPOEL, D., Sijbers, A., Keegstra, H., and Renardus, M. (1992, January 21\u201325). Gromacs-a parallel computer for molecular-dynamics simulations. Proceedings of the 4th International Conference on Computational Physics (PC 92), Annecy, France."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1107\/S0907444904011679","article-title":"PRODRG: A tool for high-throughput crystallography of protein\u2013ligand complexes","volume":"60","year":"2004","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Swamy, P.M.G., Abbas, N., Dhiwar, P.S., Singh, E., Ghara, A., and Das, A. (2021). Discovery of potential Aurora-A kinase inhibitors by 3D QSAR pharmacophore modeling, virtual screening, docking, and MD simulation studies. J. Biomol. Struct. Dyn., 1\u201322.","DOI":"10.1080\/07391102.2021.2004236"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"15317","DOI":"10.1021\/ja040968l","article-title":"Reactor ChemAxon Ltd., Maramaros koz 2\/a, Budapest, 1037 Hungary. www.chemaxon.com. Contact ChemAxon for pricing information","volume":"126","author":"Bode","year":"2004","journal-title":"J. Am. Chem. Soc."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/19\/6338\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:39:38Z","timestamp":1760143178000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/19\/6338"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,26]]},"references-count":71,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["molecules27196338"],"URL":"https:\/\/doi.org\/10.3390\/molecules27196338","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,26]]}}}