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首页> 外文会议>第三届国际分子模拟与信息技术应用学术会议 >The pharmacophore hypotheses of Ikr potassium channel blockers: novel class Ⅲ antiarrhythmic agents
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The pharmacophore hypotheses of Ikr potassium channel blockers: novel class Ⅲ antiarrhythmic agents

机译：Ikr钾通道阻滞剂的药效基团假说：新型Ⅲ类抗心律失常药

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Predictive pharmacophore models were developed for a large series of Ikr, potassium channel blockers as class Ⅲ antiarrhythmic agents using HypoGen in Catalyst software. The pharmacophore hypotheses were generated using a training set con sisting of 34 compounds carefully selected from documents. Their biological data, expressed as IC50, spanned from 1.5nM to 2.8 mM with 7 orders difference. The most predictive hypothesis (Hypol), consisting of four features (one positive ionizable feature, two aromatic rings and one hydrophobic group), had a best correlation coefficient of 0.825, a lowest rms deviation of 1.612, and a highest cost difference (null cost-total cost) of 77.552, which represents a true correlation and a good predictivity. The hypothesis Hypol was then validated by a test set consisting of 21 compounds and by a cross-validation of 95% confidence level with randomizing the data using CatScramble program. Accordingly, our model has strong predictivity to identify structural diverse Ikr potassium channel blockers with desired biological activity by virtual screening.
机译：使用Catalyst软件中的HypoGen，为Ⅲ类抗心律失常药开发了一系列Ikr，钾通道阻滞剂的预测药效团模型。药效基团假说是使用包含从文献中精心选择的34种化合物的训练集生成的。他们的生物学数据以IC50表示，范围从1.5nM到2.8 mM，相差7个数量级。最具预测性的假设（Hypol）由四个特征（一个正电离特征，两个芳环和一个疏水基团）组成，具有最佳相关系数0.825，最低rms偏差1.612和最高成本差异（零成本） （总费用）77.552，代表了真正的相关性和良好的可预测性。然后，通过由21种化合物组成的测试集和95％置信度的交叉验证对假设Hypol进行验证，并使用CatScramble程序对数据进行随机化。因此，我们的模型具有较强的可预测性，可通过虚拟筛选识别具有所需生物活性的结构多样的Ikr钾通道阻滞剂。

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