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These enzymes catalyze the reversible hydration of carbon dioxide to bicarbonate and H<jats:sup>+<\/jats:sup> ions and are thus involved in many important physiological and pathophysiological processes. Due to the fact that the human carbonic anhydrase family consists of 16 closely related isozymes, the design of selective inhibitors is a special challenge for medicinal chemists. In order to extract selectivity\u2010determining features, we applied purely ligand\u2010based 3D QSAR techniques as well as qualitative comparative molecular field analyses of the targets\u2019 binding sites using consensus principal component analysis (CPCA). The dataset for the QSAR studies was deliberately compiled from 1748 inhibitors and comprises about 140 ligands, mainly of the sulfonamide type. Additionally, we employed the novel AFMoC approach, which intrinsically combines protein and ligand information. The simultaneous use of these different techniques gives deeper insight into selectivity and affinity\u2010determining features and provides quantitative models for prediction.<\/jats:p>","DOI":"10.1002\/cmdc.200600083","type":"journal-article","created":{"date-parts":[[2006,7,10]],"date-time":"2006-07-10T13:40:15Z","timestamp":1152538815000},"page":"839-853","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Integrated Approach Using Protein and Ligand Information to Analyze Selectivity\u2010 and Affinity\u2010Determining Features of Carbonic Anhydrase Isozymes"],"prefix":"10.1002","volume":"1","author":[{"given":"Alexander","family":"Hillebrecht","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudiu\u2005T.","family":"Supuran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard","family":"Klebe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,8,3]]},"reference":[{"key":"e_1_2_5_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(96)00198-2"},{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1967.47.4.595"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.2.681"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568013013359131"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(00)00288-1"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.10.5.575"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.10025"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00226a005"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00050a010"},{"key":"e_1_2_5_10_2","first-page":"523","volume-title":"3D QSAR in Drug Design: Theory Methods and Applications, Vol.\u20051","author":"Wold S.","year":"1993"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00065a004"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm981062r"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm990250u"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00077a003"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm9800292"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm990526y"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm991164x"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00145a002"},{"key":"e_1_2_5_19_2","unstructured":"P. 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