期刊
CHEMMEDCHEM
卷 4, 期 1, 页码 100-109出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.200800274
关键词
consensus scoring; flexible docking; glucocorticoid receptor; induced-fit simulation; multidimensional QSAR
资金
- Margaret and Francis Fleitmann Foundation, Luzern (Switzerland)
- Jacques and Dolly Gazan Foundation, Zug (Switzerland)
The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily that affects immune response, development, and metabolism in target tissues. Glucocorticoids ore widely used to treat diverse pathophysiological conditions, but their clinical applicability is limited by side effects. A prediction of the binding affinity toward the GR would be beneficial for identifying glucocorticoid-mediated adverse effects triggered by drugs or chemicals. By identifying the binding mode to the GR using flexible docking (software Yeti) and quantifying the binding affinity through multidimensional QSAR (software Quasar), we validated a model family based on 110 compounds, representing four different chemical classes. The correlation with the experimental data (cross-validated r(2)=0.702; predictive r(2)=0.719) suggests that our approach is suited for predicting the binding affinity of related compounds toward the GR. After challenging the model by a series of scramble tests, a consensus approach (software Raptor), and a prediction set, it was incorporated into our VirtualToxLab and used to simulate and quantify the interaction of 24 psychotropic drugs with the GR.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据