Comparison of representational spaces based on structural information in the development of QSAR models for benzylamino enaminone derivatives

In this paper we study different representational spaces of molecule data sets based on 2D representation models for the building of QSAR models for the prediction of the activity of 37 benzylamino enaminone derivatives. Approximations based on classical similarity calculated from fingerprint representation of molecules and isomorphism obtained using sub-graph matching algorithms are compared to fragmentation-based approximations using partial least squares and genetic algorithms. The influence of the anchored position of a non-common moiety and the kind of substituents in the common core structure of the data set are analysed, demonstrating the anomalous behaviour of some molecules and therefore the difficulty in building prediction models. These problems are solved by considering approximate similarity models. These models tune the prediction equations based on the size of the substituent and the anchored position, by adjusting the contribution of each substituent in similarity measurements calculated between the molecule data sets.