Non-Linear QSAR Treatment of Genotoxicity
Mati M. Karelson, Sulev Sild, Uko Maran · Molecular Simulation · 2000
The nonlinear QSAR approach using the Chebyshev polynomial expansion and neural networks has been applied for the prediction of genotoxicity of compounds. The mutagenic toxicity of heteroaromatic and aromatic amines, measured by the Ames test, was correlated with the molecular descriptors calculated from the molecular structures using quantum-chemical methods. The quantitative models obtained were compared with the results of the linear QSAR treatment. The descriptors appearing in the models reveal the importance of mutagenic interactions of heteroaromatic amines via hydrogen bonding, of effects induced by the solvent, and of the size of compound. The dependence of molecular descriptors on environmental effects and on molecular conformations was analysed.