{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T03:13:29Z","timestamp":1779333209081,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2002,10,15]],"date-time":"2002-10-15T00:00:00Z","timestamp":1034640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2002,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although the hydrogen bond is known to be an important mediator of intermolecular interactions, there has yet to be an analysis of the role of CH\u2026O hydrogen bonds in protein\u2013ligand complexes. In this work, we present evidence for such nonstandard hydrogen bonds from a survey of aromatic ligands in 184 kinase crystal structures and 358 high\u2010resolution structures from the Protein Data Bank. CH groups adjacent to the positively charged nitrogen of nicotinamide exhibit geometric preferences strongly suggestive of hydrogen bonding interactions, as do heterocyclic CH groups in kinase ligands, while other aromatic CH groups do not exhibit these characteristics. Ab initio calculations reveal a considerable range of CH\u2026O hydrogen bonding potentials among different aromatic ring systems, with nicotinamide and heterocycles preferred in kinase inhibitors showing particularly favorable interactions. These results provide compelling evidence for the existence of CH\u2026O hydrogen bonds in protein\u2013ligand interactions, as well as information on the relative strength of various aromatic CH donors. Such knowledge will be of considerable value in protein modeling, ligand design, and structure\u2013activity analysis. Proteins 2002;49:567\u2013576. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.10259","type":"journal-article","created":{"date-parts":[[2002,10,28]],"date-time":"2002-10-28T14:38:20Z","timestamp":1035815900000},"page":"567-576","source":"Crossref","is-referenced-by-count":207,"title":["Kinase inhibitors and the case for CH\u2026O hydrogen bonds in protein\u2013ligand binding"],"prefix":"10.1002","volume":"49","author":[{"given":"Albert C.","family":"Pierce","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn L.","family":"Sandretto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy W.","family":"Bemis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,10,15]]},"reference":[{"key":"e_1_2_6_2_2","volume-title":"The weak hydrogen bond in structural chemistry and biology","author":"Desiraju GR","year":"1999"},{"key":"e_1_2_6_3_2","first-page":"459","volume-title":"Structural chemistry and molecular biology","author":"Donohue J","year":"1968"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00383a012"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00838a001"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja991795g"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar00010a002"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-1280(00)00375-4"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00064a016"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar950135n"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(01)01935-1"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.16.4843"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.1475"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.1997.10508169"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1995.0492"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.4473"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm001043t"},{"key":"e_1_2_6_18_2","doi-asserted-by":"crossref","first-page":"26157","DOI":"10.1074\/jbc.271.42.26157","article-title":"Crystal structures of catalytic subunit of cAMP\u2010dependent protein kinase in complex with isoquinolinesulfonyl protein kinase inhibitors H7, H8, H89. 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