Moorthy N S Hari Narayana, Ramos Maria J, Fernandes Pedro A
REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto , Porto , Portugal.
J Enzyme Inhib Med Chem. 2014 Jun;29(3):317-24. doi: 10.3109/14756366.2013.779264. Epub 2013 Apr 8.
In the present computational analysis, pharmacophore-based active conformer selection method was used to derive active conformers for the physicochemical descriptors calculation. The significant regression models were validated using different validation methods, which provided significant Q(2) values. The distance-based approaches were also used to analyze the discriminant property of the molecules contributed in the models. The Mahalanobis distance (MD) values obtained from these studies revealed that the compounds with very high and very low acting human ether-a-go-go-related gene blockers possessed high MD values, while the predicted activity of those compounds exhibited less residual errors. The results obtained in the studies suggest that the distance-based approaches can be used to validate the quantitative structure-activity relationship models significantly. The descriptors contributed in the models explain that the flexibility of the bonds connected to the aromatic rings or non-polar region of the molecules make π-π interaction with the aromatic residues of the protein.
在当前的计算分析中，基于药效团的活性构象体选择方法被用于推导活性构象体以进行物理化学描述符计算。使用不同的验证方法对显著回归模型进行了验证，这些方法提供了显著的Q(2)值。基于距离的方法也被用于分析模型中所涉及分子的判别特性。从这些研究中获得的马氏距离（MD）值表明，具有非常高和非常低活性的人类醚 - 去极化相关基因阻滞剂的化合物具有较高的MD值，而这些化合物的预测活性表现出较小的残差误差。研究中获得的结果表明，基于距离的方法可用于显著验证定量构效关系模型。模型中所涉及的描述符解释了与分子的芳香环或非极性区域相连的键的灵活性与蛋白质的芳香族残基发生π-π相互作用。
