Using chiral molecules as an approach to address low-druggability recognition sites
Copyright © 2014 Wiley Periodicals, Inc.
| Veröffentlicht in: | Journal of computational chemistry. - 1984. - 35(2014), 29 vom: 05. Nov., Seite 2114-21 |
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| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2014
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| Zugriff auf das übergeordnete Werk: | Journal of computational chemistry |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't chirality drug design druggability library preparation molecular recognition structural complexity Pharmaceutical Preparations Proteins mehr... |
| Zusammenfassung: | Copyright © 2014 Wiley Periodicals, Inc. 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. Herein, we present an in silico study on the yet unclear underlying correlations between molecular complexity and other more sophisticated physicochemical and biological properties. By analyzing thousands of protein-ligand complexes from DrugBank, we show that increasing molecular complexity of drugs is an approach to addressing particularly low-druggability 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. The reported results set the basis for a better understanding of protein-drug recognition, and open the possibility of including target information in the filtering of large ligand libraries for screening |
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| Beschreibung: | Date Completed 28.05.2015 Date Revised 29.09.2014 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1096-987X |
| DOI: | 10.1002/jcc.23726 |