J Mol Graph Model 2008 Apr 14;26(7):1057-65. Epub 2007 Sep 14.
Department of Chemistry, Shiraz University, Shiraz, Iran.
The usefulness of a novel type of electronic descriptors called quantum topological molecular similarity (QTMS) indices for describing the quantitative effects of molecular electronic environments on the antagonistic activity of some dihydropyridine (DHP) derivatives has been evaluated. QTMS theory produces a matrix of descriptors, including bond (or structure) information in one dimension and electronic effects in another dimension, for each molecule. Some different modeling tools such as multiple linear regression (MLR), principal component analysis (PCA), partial least squares (PLS) and genetic algorithms (GA) were employed to find some appropriate models for noted biological activity. GA was used in order to select the proper variables and also PCA was used for data compression. Then modeling was performed by MLR and PLS. The model performances were accessed by both cross-validation and external prediction set. The results showed that the proposed models could explain above 90% of variances in the biological activity. The significant effects of chemical bonds on the antagonistic activity were identified by calculating variable important in projection (VIP). It was obtained that those belonging to the substituted 4-phenyl ring represent high influence on the biological activity which, confirms their importance in mechanism of action of DHP derivatives.