{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T05:10:29Z","timestamp":1696482629516},"reference-count":27,"publisher":"Wiley","issue":"29","license":[{"start":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T00:00:00Z","timestamp":1410825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Excellence Initiative of the German Federal and State Governments through the Junior Research Group Program","award":["ZUK 43 (SG)"],"award-info":[{"award-number":["ZUK 43 (SG)"]}]},{"name":"Federal State of Baden-W\u00fcrttemberg (Ministry of Arts and Science) through the \u201cZukunftsoffensive IV (ZO IV) Juniorprofessoren-Programm\u201d (XL)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Comput Chem"],"published-print":{"date-parts":[[2014,11,5]]},"abstract":"<jats:p>The content of chiral carbon atoms or structural complexity, which is known to correlate well with relevant physicochemical properties of small molecules, represents a promising descriptor that could fill the gap in existing drug discovery between ligand library filtering rules and the corresponding properties of the target's recognition site.<\/jats:p><jats:p>Herein, we present an <jats:italic>in silico<\/jats:italic> study on the yet unclear underlying correlations between molecular complexity and other more sophisticated physicochemical and biological properties. By analyzing thousands of protein\u2013ligand complexes from DrugBank, we show that increasing molecular complexity of drugs is an approach to addressing particularly low\u2010druggability and polar recognition sites. We also show that biologically relevant protein classes characteristically bind molecules with a certain degree of structural complexity. Three distinct behaviors toward drug recognition are described.<\/jats:p><jats:p>The reported results set the basis for a better understanding of protein\u2013drug recognition, and open the possibility of including target information in the filtering of large ligand libraries for screening. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcc.23726","type":"journal-article","created":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T10:38:01Z","timestamp":1410863881000},"page":"2114-2121","source":"Crossref","is-referenced-by-count":4,"title":["Using chiral molecules as an approach to address low\u2010druggability recognition sites"],"prefix":"10.1002","volume":"35","author":[{"given":"Xavier","family":"Lucas","sequence":"first","affiliation":[{"name":"Pharmaceutical Bioinformatics, Institute of Pharmaceutical Sciences, University of Freiburg 79104 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Pharmaceutical Bioinformatics, Institute of Pharmaceutical Sciences, University of Freiburg 79104 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,9,16]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2013.04.018"},{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2013.01.007"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12054"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201307652"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm901137j"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.112.005660"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1056-8719(00)00107-6"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026611313090010"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci000403i"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2011.05.008"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1012741107"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm901241e"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1126"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-3-33"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth214"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct200133y"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1223"},{"key":"e_1_2_6_18_1","unstructured":"R Core Team R Foundation for Statistical Computing Vienna Austria 2013."},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161212799436386"},{"key":"e_1_2_6_20_1","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/978-1-61779-520-6_15","volume":"841","author":"Maddaford S. 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