دورية أكاديمية
Systematic exploitation of multiple receptor conformations for virtual ligand screening.
| العنوان: | Systematic exploitation of multiple receptor conformations for virtual ligand screening. |
|---|---|
| المؤلفون: | Giovanni Bottegoni, Walter Rocchia, Manuel Rueda, Ruben Abagyan, Andrea Cavalli |
| المصدر: | PLoS ONE, Vol 6, Iss 5, p e18845 (2011) |
| بيانات النشر: | Public Library of Science (PLoS), 2011. |
| سنة النشر: | 2011 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | The role of virtual ligand screening in modern drug discovery is to mine large chemical collections and to prioritize for experimental testing a comparatively small and diverse set of compounds with expected activity against a target. Several studies have pointed out that the performance of virtual ligand screening can be improved by taking into account receptor flexibility. Here, we systematically assess how multiple crystallographic receptor conformations, a powerful way of discretely representing protein plasticity, can be exploited in screening protocols to separate binders from non-binders. Our analyses encompass 36 targets of pharmaceutical relevance and are based on actual molecules with reported activity against those targets. The results suggest that an ensemble receptor-based protocol displays a stronger discriminating power between active and inactive molecules as compared to its standard single rigid receptor counterpart. Moreover, such a protocol can be engineered not only to enrich a higher number of active compounds, but also to enhance their chemical diversity. Finally, some clear indications can be gathered on how to select a subset of receptor conformations that is most likely to provide the best performance in a real life scenario. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| العلاقة: | http://europepmc.org/articles/PMC3098722?pdf=renderTest; https://doaj.org/toc/1932-6203Test |
| DOI: | 10.1371/journal.pone.0018845 |
| الوصول الحر: | https://doaj.org/article/94f12c65bb8a49d5b277e07ddf1d2687Test |
| رقم الانضمام: | edsdoj.94f12c65bb8a49d5b277e07ddf1d2687 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
|---|---|
| DOI: | 10.1371/journal.pone.0018845 |