{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T14:20:24Z","timestamp":1770992424820,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,6,23]],"date-time":"2018-06-23T00:00:00Z","timestamp":1529712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Carbonic anhydrase II (CAII) is a zinc-containing metalloenzyme whose aberrant activity is associated with various diseases such as glaucoma, osteoporosis, and different types of tumors; therefore, the development of CAII inhibitors, which can represent promising therapeutic agents for the treatment of these pathologies, is a current topic in medicinal chemistry. Molecular docking is a commonly used tool in structure-based drug design of enzyme inhibitors. However, there is still a need for improving docking reliability, especially in terms of scoring functions, since the complex pattern of energetic contributions driving ligand\u2013protein binding cannot be properly described by mathematical functions only including approximated energetic terms. Here we report a novel CAII-specific fingerprint-based (IFP) scoring function developed according to the ligand\u2013protein interactions detected in the CAII-inhibitor co-crystal structures of the most potent CAII ligands. Our IFP scoring function outperformed the ability of Autodock4 scoring function to identify native-like docking poses of CAII inhibitors and thus allowed a considerable improvement of docking reliability. Moreover, the ligand\u2013protein interaction fingerprints showed a useful application in the binding mode analysis of structurally diverse CAII ligands.<\/jats:p>","DOI":"10.3390\/ijms19071851","type":"journal-article","created":{"date-parts":[[2018,6,25]],"date-time":"2018-06-25T11:03:25Z","timestamp":1529924605000},"page":"1851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Development of a Fingerprint-Based Scoring Function for the Prediction of the Binding Mode of Carbonic Anhydrase II Inhibitors"],"prefix":"10.3390","volume":"19","author":[{"given":"Giulio","family":"Poli","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1168-7480","authenticated-orcid":false,"given":"Vibhu","family":"Jha","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7197-0552","authenticated-orcid":false,"given":"Adriano","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4262-0323","authenticated-orcid":false,"given":"Claudiu T.","family":"Supuran","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Universit\u00e0 degli Studi di Firenze, Sesto Fiorentino, 50019 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6205-4069","authenticated-orcid":false,"given":"Tiziano","family":"Tuccinardi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,6,23]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1016\/j.ejmech.2017.11.005","article-title":"Novel 2-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl)-1-(1,3,5-triazin-2-ylamino)guanidine derivatives: Inhibition of human carbonic anhydrase cytosolic isozymes I and II and the transmembrane tumor-associated isozymes IX and XII, anticancer activit","volume":"143","author":"Angeli","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1042\/BCJ20160115","article-title":"Structure and function of carbonic anhydrases","volume":"473","author":"Supuran","year":"2016","journal-title":"Biochem. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.ejmech.2018.03.030","article-title":"Synthesis of novel 4-functionalized 1,5-diaryl-1,2,3-triazoles containing benzenesulfonamide moiety as carbonic anhydrase I, II, IV and IX inhibitors","volume":"150","author":"Vats","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1080\/14756366.2017.1284069","article-title":"Biochemical characterization of the native \u03b1-carbonic anhydrase purified from the mantle of the Mediterranean mussel, Mytilus galloprovincialis","volume":"32","author":"Perfetto","year":"2017","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3109\/14756366.2013.761876","article-title":"Carbonic anhydrases: From biomedical applications of the inhibitors and activators to biotechnological use for CO2capture","volume":"28","author":"Supuran","year":"2013","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1215\/15228517-2007-001","article-title":"Carbonic anhydrase II in the endothelium of glial tumors: A potential target for therapy","volume":"9","author":"Haapasalo","year":"2007","journal-title":"Neuro. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.ejmech.2015.06.022","article-title":"Probing the \u201cbipolar\u201d nature of the carbonic anhydrase active site: Aromatic sulfonamides containing 1,3-oxazol-5-yl moiety as picomolar inhibitors of cytosolic CA I and CA II isoforms","volume":"101","author":"Krasavin","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"303","DOI":"10.2174\/138620709787581666","article-title":"Docking-Based Virtual Screening: Recent Developments","volume":"12","author":"Tuccinardi","year":"2009","journal-title":"Comb. Chem. High Throughput Screen."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1021\/ci500319f","article-title":"Structural protein-ligand interaction fingerprints (SPLIF) for structure-based virtual screening: Method and benchmark study","volume":"54","author":"Da","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Liu, J., Su, M., Liu, Z., Li, J., Li, Y., and Wang, R. (2017). Enhance the performance of current scoring functions with the aid of 3D protein-ligand interaction fingerprints. BMC Bioinform., 18.","DOI":"10.1186\/s12859-017-1750-5"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1021\/ci600342e","article-title":"Optimizing fragment and scaffold docking by use of molecular interaction fingerprints","volume":"47","author":"Marcou","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1107\/S0907444902003451","article-title":"The protein data bank","volume":"58","author":"Berman","year":"2002","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1021\/ci500424n","article-title":"Extensive consensus docking evaluation for ligand pose prediction and virtual screening studies","volume":"54","author":"Tuccinardi","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/14756366.2016.1193736","article-title":"Reliability analysis and optimization of the consensus docking approach for the development of virtual screening studies","volume":"31","author":"Poli","year":"2016","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.jmgm.2011.01.004","article-title":"BINANA: A novel algorithm for ligand-binding characterization","volume":"29","author":"Durrant","year":"2011","journal-title":"J. Mol. Graph. Model."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1021\/jm400378w","article-title":"KLIFS: A knowledge-based structural database to navigate kinase-ligand interaction space","volume":"57","author":"Kooistra","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7029","DOI":"10.1021\/acs.jmedchem.5b01813","article-title":"PDEStrIAn: A Phosphodiesterase Structure and Ligand Interaction Annotated Database As a Tool for Structure-Based Drug Design","volume":"59","author":"Jansen","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_20","unstructured":"(2018, May 02). Maestro, Version 10.6. Available online: https:\/\/www.schrodinger.com\/."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rostkowski, M., Olsson, M.H., S\u00f8ndergaard, C.R., and Jensen, J.H. (2011). Graphical analysis of pH-dependent properties of proteins predicted using PROPKA. BMC Struct. Biol., 11.","DOI":"10.1186\/1472-6807-11-6"},{"key":"ref_22","unstructured":"(2018, May 02). Macromodel, Version 9.7. Available online: https:\/\/www.schrodinger.com\/."},{"key":"ref_23","first-page":"57","article-title":"Python: A programming language for software integration and development","volume":"17","author":"Sanner","year":"1999","journal-title":"J. Mol. Graph. Model."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1021\/ci500209e","article-title":"AutoDock4Zn: An improved AutoDock force field for small-molecule docking to zinc metalloproteins","volume":"54","author":"Forli","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1021\/ci600469w","article-title":"Analysis of human carbonic anhydrase II: Docking reliability and receptor-based 3D-QSAR study","volume":"47","author":"Tuccinardi","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/prot.10465","article-title":"Improved protein-ligand docking using GOLD","volume":"52","author":"Verdonk","year":"2003","journal-title":"Proteins Struct. Funct. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1021\/ci5006806","article-title":"Application of a FLAP-consensus docking mixed strategy for the identification of new fatty acid amide hydrolase inhibitors","volume":"55","author":"Poli","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3285","DOI":"10.1016\/j.bmc.2014.04.057","article-title":"Identification and characterization of a new reversible MAGL inhibitor","volume":"22","author":"Tuccinardi","year":"2014","journal-title":"Bioorganic Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.3109\/14756366.2015.1079184","article-title":"Identification of a new STAT3 dimerization inhibitor through a pharmacophore-based virtual screening approach","volume":"31","author":"Poli","year":"2016","journal-title":"J. Enzyme Inhib. Med. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/7\/1851\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:09:53Z","timestamp":1760195393000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/7\/1851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,23]]},"references-count":30,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2018,7]]}},"alternative-id":["ijms19071851"],"URL":"https:\/\/doi.org\/10.3390\/ijms19071851","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,23]]}}}