Toropov Andrey A, Benfenati Emilio
Laboratory of Environmental Chemistry and Toxicology, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milan, Italy.
Bioorg Med Chem. 2006 Apr 15;14(8):2779-88. doi: 10.1016/j.bmc.2005.11.060. Epub 2005 Dec 27.
A topological parameter is defined as an integer value of a given local or global invariant of a molecular graph. We examined three types of local graph invariants, the vertex degrees (0EC), the extended connectivity of first order (1EC), and the numbers of paths of length two (P2), as elementary invariants for construction of quantitative structure-activity relationships (QSAR). We also examined combined invariants, obtained by multiplying one of these three elementary types with another (i.e., [0EC.1EC], [0EC.P2], and [1EC.P2]), as graph invariants. Finally, global invariants were used in the QSAR analyses, codifying the presence and nature of cycles in the molecular structures under consideration. We used the correlation weights of these invariants to obtain optimal descriptors. These descriptors have been used in one-variable models to predict toxicity toward Daphnia magna for a set of pesticides. Statistical characteristics of the best model, based on the correlation weight of local topological parameters (the [0EC.P2]) together with the global topological parameters, are the following: n=220, r2=0.7822, s=0.849, F=783 (training set); n=42, r2=0.7388, s=0.941, F=113 (test set). The role of these topological parameters is discussed.
拓扑参数被定义为分子图给定局部或全局不变量的整数值。我们研究了三种局部图不变量，即顶点度（0EC）、一阶扩展连通性（1EC）和长度为二的路径数（P2），作为构建定量构效关系（QSAR）的基本不变量。我们还研究了通过将这三种基本类型中的一种与另一种相乘得到的组合不变量（即[0EC.1EC]、[0EC.P2]和[1EC.P2]），作为图不变量。最后，在QSAR分析中使用全局不变量，对所考虑分子结构中环的存在和性质进行编码。我们使用这些不变量的相关权重来获得最佳描述符。这些描述符已用于单变量模型中，以预测一组农药对大型溞的毒性。基于局部拓扑参数（[0EC.P2]）与全局拓扑参数的相关权重的最佳模型的统计特征如下：n = 220，r2 = 0.7822，s = 0.849，F = 783（训练集）；n = 42，r2 = 0.7388，s = 0.941，F = 113（测试集）。讨论了这些拓扑参数的作用。
