Three-dimensional quantitative similarity-activity relationships (3D QSiAR) from SEAL similarity matrices
Three-dimensional quantitative similarity-activity relationships (3D QSiAR) from SEAL similarity matrices
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DOI：
10.1021/jm970732a
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发表时间：
1998-07-02
影响因子：
7.3
通讯作者：
Mietzner, T
中科院分区：
文献类型：
--
作者：
Kubinyi, H;Hamprecht, FA;Mietzner, T
SEAL程序适用于定量描述不同分子的静电、立体、疏水和氢键供体和受体的相似性。相似性分数AF可以计算成对分子，使用某种分子性质或加权性质的总和。或者，它们的相互相似性可以从在规则网格中计算的基于seal的属性字段之间的距离d或协方差c派生。对于一组N个化学相关分子，这些值形成一个N × N的相似性矩阵，可以使用回归分析和适当的变量选择程序或偏最小二乘（PLS）分析与生物活性相关。对于Cramer类固醇数据集，基于分子性质加权和的不同PLS模型的测试集预测(r（pred)(2) = 0.53-0.84）优于CoMFA和CoMSIA研究的已发表结果(r(pred)(2) = 0.31-0.40)，无论所有分子的共同排列还是个体，两两排列都用于计算相似性矩阵。训练集和测试集的选择对模型的外部预测能力有显著影响。虽然两个分子之间的SEAL相似度得分是一个单一的数字，但它的值是基于两个分子的三维性质。术语3D定量相似活性分析（3D QSiAR）被提出用于将3D结构衍生的相似性矩阵与生物活性相关联的方法。
The program SEAL is suited to describe the electrostatic, steric, hydrophobic, and hydrogen bond donor and acceptor similarity of different molecules in a quantitative manner. Similarity scores AF can be calculated for pairs of molecules, using either a certain molecular property or a sum of weighted properties. Alternatively, their mutual similarity can be derived from distances d or covariances c between SEAL-based property fields that are calculated in a regular grid. For a set of N chemically related molecules, such values form an N x N similarity matrix which can be correlated with biological activities, using either regression analysis and an appropriate variable selection procedure or partial least-squares (PLS) analysis. For the Cramer steroid data set, the test set predictivities (r(pred)(2) = 0.53-0.84) of different PLS models, based on a weighted sum of molecular properties, are superior to published results of CoMFA and CoMSIA studies (r(pred)(2) = 0.31-0.40), regardless of whether a common alignment or individual, pairwise alignments of all molecules are used in the calculation of the similarity matrices. Training and test set selections have a significant influence on the external predictivities of the models. Although the SEAL similarity score between two molecules is a single number, its value is based on the 3D properties of both molecules. The term 3D quantitative similarity-activity analyses (3D QSiAR) is proposed for approaches which correlate 3D structure-derived similarity matrices with biological activities.