{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T14:17:57Z","timestamp":1781705877379,"version":"3.54.5"},"reference-count":70,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T00:00:00Z","timestamp":1691539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["21977013"],"award-info":[{"award-number":["21977013"]}]},{"name":"National Natural Science Foundation of China","award":["21606016"],"award-info":[{"award-number":["21606016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human carbonic anhydrases (hCAs) have enzymatic activities for reversible hydration of CO2 and are acknowledged as promising targets for the treatment of various diseases. Using molecular docking and molecular dynamics simulation approaches, we hit three compounds of methyl 4-chloranyl-2-(phenylsulfonyl)-5-sulfamoyl-benzoate (84Z for short), cyclothiazide, and 2,3,5,6-tetrafluoro-4-piperidin-1-ylbenzenesulfonamide (3UG for short) from the existing hCA I inhibitors and word-approved drugs. As a Zn2+-dependent metallo-enzyme, the influence of Zn2+ ion models on the stability of metal-binding sites during MD simulations was addressed as well. MM-PBSA analysis predicted a strong binding affinity of \u221218, \u221216, and \u221214 kcal\/mol, respectively, for these compounds, and identified key protein residues for binding. The sulfonamide moiety bound to the Zn2+ ion appeared as an essential component of hCA I inhibitors. Vina software predicted a relatively large (unreasonable) Zn2+\u2013sulfonamide distance, although the relative binding strength was reproduced with good accuracy. The selected compounds displayed potent inhibition against other hCA isoforms of II, XIII, and XIV. This work is valuable for molecular modeling of hCAs and further design of potent inhibitors.<\/jats:p>","DOI":"10.3390\/ijms241612619","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T10:08:59Z","timestamp":1691575739000},"page":"12619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Repurposing of World-Approved Drugs for Potential Inhibition against Human Carbonic Anhydrase I: A Computational Study"],"prefix":"10.3390","volume":"24","author":[{"given":"Nannan","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Biological Science and Engineering, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4680-0623","authenticated-orcid":false,"given":"Wanyun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Engineering, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Engineering, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Engineering, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6298-3186","authenticated-orcid":false,"given":"Junzhao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Engineering, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2410-7078","authenticated-orcid":false,"given":"Haiyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Engineering, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1016\/j.bmc.2012.04.044","article-title":"Structure, function and applications of carbonic anhydrase isozymes","volume":"21","author":"Hassan","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1517\/17425255.2.1.113","article-title":"A perspective on quantitative structure\u2013activity relationships and carbonic anhydrase inhibitors","volume":"2","author":"Clare","year":"2006","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1080\/14756360410001689540","article-title":"Carbonic anhydrases: Current state of the art, therapeutic applications and future prospects","volume":"19","author":"Pastorekova","year":"2004","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Moi, D., Vittorio, S., Angeli, A., Balboni, G., Supuran, C.T., and Onnis, V. (2022). Investigation on Hydrazonobenzenesulfonamides as Human Carbonic Anhydrase I, II, IX and XII Inhibitors. Molecules, 28.","DOI":"10.3390\/molecules28010091"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"759","DOI":"10.3109\/14756366.2012.672983","article-title":"Structure-based drug discovery of carbonic anhydrase inhibitors","volume":"27","author":"Supuran","year":"2012","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0163-7258(96)00198-2","article-title":"Structure and mechanism of carbonic anhydrase","volume":"74","author":"Lindskog","year":"1997","journal-title":"Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Langella, E., Esposito, D., Monti, S.M., Supuran, C.T., De Simone, G., and Alterio, V. (2023). A Combined in Silico and Structural Study Opens New Perspectives on Aliphatic Sulfonamides, a Still Poorly Investigated Class of CA Inhibitors. Biology, 12.","DOI":"10.3390\/biology12020281"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1464-410X.2008.07642.x","article-title":"Molecular mechanisms of carbonic anhydrase IX-mediated pH regulation under hypoxia","volume":"101","author":"Pastorekova","year":"2008","journal-title":"BJU Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/978-94-007-7359-2_17","article-title":"Glaucoma and the Applications of Carbonic Anhydrase Inhibitors","volume":"75","author":"Scozzafava","year":"2013","journal-title":"Subcell Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.atherosclerosis.2015.05.012","article-title":"The role of carbonic anhydrase in the pathogenesis of vascular calcification in humans","volume":"241","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1097\/j.pain.0000000000002627","article-title":"Hypoxia-induced carbonic anhydrase mediated dorsal horn neuron activation and induction of neuropathic pain","volume":"163","author":"Lobo","year":"2022","journal-title":"Pain"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/j.1747-0285.2009.00857.x","article-title":"Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates?","volume":"74","author":"Scozzafava","year":"2009","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"354594","DOI":"10.1155\/2012\/354594","article-title":"Carbonic Anhydrases III and IV Autoantibodies in Rheumatoid Arthritis, Systemic Lupus Erythematosus, Diabetes, Hypertensive Renal Disease, and Heart Failure","volume":"2012","author":"Liu","year":"2012","journal-title":"Clin. Dev. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1080\/14737175.2016.1193009","article-title":"Carbonic anhydrase inhibition and the management of neuropathic pain","volume":"16","author":"Supuran","year":"2016","journal-title":"Expert Rev. Neurother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16233","DOI":"10.1073\/pnas.0908301106","article-title":"Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX","volume":"106","author":"Alterio","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"821","DOI":"10.2174\/092986712799034851","article-title":"Carbonic Anhydrase IX as a Target for Designing Novel Anticancer Drugs","volume":"19","author":"Monti","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1042\/CS20210040","article-title":"Emerging role of carbonic anhydrase inhibitors","volume":"135","author":"Supuran","year":"2021","journal-title":"Clin. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9101","DOI":"10.1016\/j.bmc.2008.09.028","article-title":"In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II","volume":"16","author":"Bayram","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zak\u0161auskas, A., \u010capkauskait\u0117, E., Paketuryt\u0117-Latv\u0117, V., Smirnov, A., Leitans, J., Kazaks, A., Dvinskis, E., Stan\u010daitis, L., Mickevi\u010di\u016bt\u0117, A., and Jachno, J. (2021). Methyl 2-Halo-4-Substituted-5-Sulfamoyl-Benzoates as High Affinity and Selective Inhibitors of Carbonic Anhydrase IX. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010130"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"105888","DOI":"10.1016\/j.bioorg.2022.105888","article-title":"Insights into the effect of elaborating coumarin-based aryl enaminones with sulfonamide or carboxylic acid functionality on carbonic anhydrase inhibitory potency and selectivity","volume":"126","author":"Ibrahim","year":"2022","journal-title":"Bioorg. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1016\/j.bmc.2014.12.054","article-title":"N-Acylsulfonamides strongly inhibit human carbonic anhydrase isoenzymes I and II","volume":"23","author":"Atmaca","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/j.bmc.2013.01.019","article-title":"Novel sulfamides as potential carbonic anhydrase isoenzymes inhibitors","volume":"21","author":"Akbaba","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3467","DOI":"10.1016\/j.bmcl.2010.05.009","article-title":"Carbonic anhydrase inhibitors","volume":"20","author":"Supuran","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1080\/17460441.2021.1922384","article-title":"Advances in the discovery of novel agents for the treatment of glaucoma","volume":"16","author":"Mincione","year":"2021","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1016\/j.bmc.2012.06.053","article-title":"Effect of sulfonamides as carbonic anhydrase VA and VB inhibitors on mitochondrial metabolic energy conversion","volume":"21","author":"Arechederra","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1080\/14756366.2022.2121393","article-title":"Anti-obesity carbonic anhydrase inhibitors: Challenges and opportunities","volume":"37","author":"Supuran","year":"2022","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.1158\/0008-5472.CAN-10-4261","article-title":"Targeting Tumor Hypoxia: Suppression of Breast Tumor Growth and Metastasis by Novel Carbonic Anhydrase IX Inhibitors","volume":"71","author":"Lou","year":"2011","journal-title":"Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7558","DOI":"10.1158\/0008-5472.CAN-11-2520","article-title":"Phosphorylation of Carbonic Anhydrase IX Controls Its Ability to Mediate Extracellular Acidification in Hypoxic Tumors","volume":"71","author":"Ditte","year":"2011","journal-title":"Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.tetlet.2016.12.005","article-title":"Synthesis, structure and properties of N -aminosaccharin\u2014A selective inhibitor of human carbonic anhydrase I","volume":"58","author":"Kuznetsov","year":"2016","journal-title":"Tetrahedron Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5801","DOI":"10.1016\/j.bmcl.2012.07.094","article-title":"Inhibition of alpha-class cytosolic human carbonic anhydrases I, II, IX and XII, and beta-class fungal enzymes by carboxylic acids and their derivatives: New isoform-I selective nanomolar inhibitors","volume":"22","author":"Sechi","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nm1534","article-title":"Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation","volume":"13","author":"Gao","year":"2007","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1007\/s13205-018-1278-z","article-title":"Designing of phenol-based beta-carbonic anhydrase1 inhibitors through QSAR, molecular docking, and MD simulation approach","volume":"8","author":"Ahamad","year":"2018","journal-title":"3 Biotech"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Berrino, E., Bua, S., Mori, M., Botta, M., Murthy, V.S., Vijayakumar, V., Tamboli, Y., Bartolucci, G., Mugelli, A., and Cerbai, E. (2017). Novel Sulfamide-Containing Compounds as Selective Carbonic Anhydrase I Inhibitors. Molecules, 22.","DOI":"10.3390\/molecules22071049"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.molstruc.2015.10.054","article-title":"Carbonic anhydrase inhibitors: Synthesis, characterization and inhibition activities of furan sulfonylhydrazones against carbonic anhydrase I (hCA I)","volume":"1105","author":"Uzun","year":"2016","journal-title":"J. Mol. Struct."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1080\/14756366.2016.1235043","article-title":"Carbonic anhydrase inhibitory properties of some uracil derivatives","volume":"32","author":"Supuran","year":"2017","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3790","DOI":"10.1016\/j.bmc.2013.04.041","article-title":"Natural product hybrid and its superacid synthesized analogues: Dodoneine and its derivatives show selective inhibition of carbonic anhydrase isoforms I, III, XIII and XIV","volume":"21","author":"Carreyre","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3109\/14756366.2011.578393","article-title":"Carbonic anhydrase I and II inhibition with natural products: Caffeine and piperine","volume":"27","author":"Sethi","year":"2011","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_38","first-page":"594","article-title":"Synthesis of 4-[2-(3,4-dimethoxybenzyl)cyclopentyl]-1,2-dimethoxybenzene Derivatives and Evaluations of Their Carbonic Anhydrase Isoenzymes Inhibitory Effects","volume":"87","author":"Menzek","year":"2015","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0960-894X(03)00029-5","article-title":"Carbonic anhydrase inhibitors: SAR and X-ray crystallographic study for the interaction of sugar sulfamates\/sulfamides with isozymes I, II and IV","volume":"13","author":"Casini","year":"2003","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4873","DOI":"10.1016\/j.bmc.2010.06.028","article-title":"Coumarinyl-substituted sulfonamides strongly inhibit several human carbonic anhydrase isoforms: Solution and crystallographic investigations","volume":"18","author":"Wagner","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.2174\/138161210793429797","article-title":"Carbonic Anhydrase Inhibition\/Activation: Trip of a Scientist Around the World in the Search of Novel Chemotypes and Drug Targets","volume":"16","author":"Supuran","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1016\/j.bmc.2012.05.019","article-title":"Mono-\/dihydroxybenzoic acid esters and phenol pyridinium derivatives as inhibitors of the mammalian carbonic anhydrase isoforms I, II, VII, IX, XII and XIV","volume":"21","author":"Carta","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.bmcl.2011.11.018","article-title":"5- and 6-Membered (thio)lactones are prodrug type carbonic anhydrase inhibitors","volume":"22","author":"Carta","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1016\/j.bmcl.2012.01.129","article-title":"New chemotypes acting as isozyme-selective carbonic anhydrase inhibitors with low affinity for the offtarget cytosolic isoform II","volume":"22","author":"Carta","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1517\/17460441.2013.795145","article-title":"Exploiting the hydrophobic and hydrophilic binding sites for designing carbonic anhydrase inhibitors","volume":"8","author":"Alterio","year":"2013","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.1021\/jm0603320","article-title":"Carbonic anhydrase activators. Activation of isoforms I, II, IV, VA, VII, and XIV with L- and D-phenylalanine and crystallographic analysis of their adducts with isozyme II: Stereospecific recognition within the active site of an enzyme and its consequences for the drug design","volume":"49","author":"Temperini","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1016\/j.bmc.2011.01.016","article-title":"Kinetic and docking studies of phenol-based inhibitors of carbonic anhydrase isoforms I, II, IX and XII evidence a new binding mode within the enzyme active site","volume":"19","author":"Durdagi","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.2174\/09298673113209990001","article-title":"Virtual screening strategies in drug discovery: A critical review","volume":"20","author":"Lavecchia","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrd.2018.168","article-title":"Drug repurposing: Progress, challenges and recommendations","volume":"18","author":"Pushpakom","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1021\/ja00002a004","article-title":"Carbon dioxide binding to human carbonic anhydrase II","volume":"113","author":"Merz","year":"1991","journal-title":"J. Am. Chem. Soc."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1021\/ct400751u","article-title":"Taking into Account the Ion-Induced Dipole Interaction in the Nonbonded Model of Ions","volume":"10","author":"Li","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4031","DOI":"10.1021\/acs.jcim.1c00580","article-title":"Rational Design of Nonbonded Point Charge Models for Divalent Metal Cations with Lennard-Jones 12-6 Potential","volume":"61","author":"Zhang","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3803","DOI":"10.1021\/acs.jcim.9b00407","article-title":"Upgrading and Validation of the AMBER Force Field for Histidine and Cysteine Zinc(II)-Binding Residues in Sites with Four Protein Ligands","volume":"59","author":"Macchiagodena","year":"2019","journal-title":"J. Chem. Inf. Model."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15301","DOI":"10.1021\/acsomega.0c01337","article-title":"Upgraded AMBER Force Field for Zinc-Binding Residues and Ligands for Predicting Structural Properties and Binding Affinities in Zinc-Proteins","volume":"5","author":"Macchiagodena","year":"2020","journal-title":"ACS Omega"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1021\/acs.jcim.5b00559","article-title":"ZINC 15\u2014Ligand Discovery for Everyone","volume":"55","author":"Sterling","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"W257","DOI":"10.1093\/nar\/gky318","article-title":"ProTox-II: A webserver for the prediction of toxicity of chemicals","volume":"46","author":"Banerjee","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1002\/jcc.27052","article-title":"Benchmarking biomolecular force field-based Zn2+ for mono- and bimetallic ligand binding sites","volume":"44","author":"Melse","year":"2023","journal-title":"J. Comput. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1002\/prot.22711","article-title":"Improved side-chain torsion potentials for the Amber ff99SB protein force field","volume":"78","author":"Piana","year":"2010","journal-title":"Proteins"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"ref_61","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","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Zhou, B., Zhang, Y., Jiang, W., and Zhang, H. (2022). Virtual Screening of FDA-Approved Drugs for Enhanced Binding with Mitochondrial Aldehyde Dehydrogenase. Molecules, 27.","DOI":"10.3390\/molecules27248773"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"8115","DOI":"10.1021\/acsomega.2c00032","article-title":"Computational Investigation of Structural Basis for Enhanced Binding of Isoflavone Analogues with Mitochondrial Aldehyde Dehydrogenase","volume":"7","author":"Zhang","year":"2022","journal-title":"ACS Omega"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development and testing of a general amber force field","volume":"25","author":"Wang","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_65","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., and Petersson, G.A. (2009). Gaussian 09, Gaussian, Inc.. Revision B.01."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6281","DOI":"10.1021\/acs.jctc.1c00645","article-title":"gmx_MMPBSA: A New Tool to Perform End-State Free Energy Calculations with GROMACS","volume":"17","author":"Valiente","year":"2021","journal-title":"J. Chem. Theory Comput."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1021\/ct300418h","article-title":"MMPBSA.py: An Efficient Program for End-State Free Energy Calculations","volume":"8","author":"Miller","year":"2012","journal-title":"J. Chem. Theory Comput."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4421","DOI":"10.1021\/cr200176r","article-title":"Multiple Binding Modes of Inhibitors to Carbonic Anhydrases: How to Design Specific Drugs Targeting 15 Different Isoforms?","volume":"112","author":"Alterio","year":"2012","journal-title":"Chem. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrd2467","article-title":"Carbonic anhydrases: Novel therapeutic applications for inhibitors and activators","volume":"7","author":"Supuran","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_70","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"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/16\/12619\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:29:53Z","timestamp":1760128193000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/16\/12619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,9]]},"references-count":70,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["ijms241612619"],"URL":"https:\/\/doi.org\/10.3390\/ijms241612619","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,9]]}}}