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Although activity cliffs are mostly studied in medicinal chemistry at the level of molecular graphs, they can also be assessed by comparing compound binding modes. If such three\u2010dimensional activity cliffs (3<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>\u2010cliffs) are studied on the basis of <jats:styled-content style=\"fixed-case\">X<\/jats:styled-content>\u2010ray complex structures, experimental ligand\u2013target interaction details can be taken into account. Rapid growth in the number of 3<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>\u2010cliffs that can be derived from <jats:styled-content style=\"fixed-case\">X<\/jats:styled-content>\u2010ray complex structures has made it possible to identify targets for which a substantial body of 3<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>\u2010cliff information is available. Activity cliffs are typically studied to identify structure\u2013activity relationship determinants and aid in compound optimization. However, 3<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>\u2010cliff information can also be used to search for interaction hot spots and key residues, as reported herein. For six of seven drug targets for which more than 20 3<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>\u2010cliffs were available, series of 3<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>\u2010cliffs were identified that were consistently involved in interactions with different hot spots. These 3<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>\u2010cliffs often encoded chemical modifications resulting in interactions that were characteristic of highly potent compounds but absent in weakly potent ones, thus providing information for structure\u2010based design.<\/jats:p>","DOI":"10.1111\/cbdd.12605","type":"journal-article","created":{"date-parts":[[2015,6,19]],"date-time":"2015-06-19T22:51:07Z","timestamp":1434754267000},"page":"1458-1465","source":"Crossref","is-referenced-by-count":9,"title":["Identification of Interaction Hot Spots in Structures of Drug Targets on the Basis of Three\u2010Dimensional Activity Cliff Information"],"prefix":"10.1111","volume":"86","author":[{"given":"Norbert","family":"Furtmann","sequence":"first","affiliation":[{"name":"Department of Life Science Informatics B\u2010IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry Rheinische Friedrich\u2010Wilhelms\u2010Universit\u00e4t Dahlmannstr. 2 D\u201053113 Bonn Germany"},{"name":"Pharmaceutical Institute University of Bonn An der Immenburg 4 D\u201053121 Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Life Science Informatics B\u2010IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry Rheinische Friedrich\u2010Wilhelms\u2010Universit\u00e4t Dahlmannstr. 2 D\u201053113 Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"G\u00fctschow","sequence":"additional","affiliation":[{"name":"Pharmaceutical Institute University of Bonn An der Immenburg 4 D\u201053121 Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Bajorath","sequence":"additional","affiliation":[{"name":"Department of Life Science Informatics B\u2010IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry Rheinische Friedrich\u2010Wilhelms\u2010Universit\u00e4t Dahlmannstr. 2 D\u201053113 Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,7,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci060117s"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm201706b"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm401120g"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm401411z"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci800379q"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci3001138"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201100179"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci300033e"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2007.03.011"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci300158v"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5RA01730K"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4163"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr777"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp846"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-014-9567-x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-062209-095159"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm100146h"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70276-X"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2013.784267"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2013.735228"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R400027200"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2007.04.020"},{"key":"e_1_2_8_25_1","first-page":"419","article-title":"Carbonic\u2010anhydrase isoenzymes Ca\u2010I and Ca\u2010II in the human\u2010eye","volume":"27","author":"Wistrand P.J.","year":"1986","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.040554897"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.03.7689"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.09.102"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.18527"}],"container-title":["Chemical Biology &amp; 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