On machine learning based QSPR analysis of amphetamine derivatives using regression models

In this study, we show the quantitative structure-property relationship (QSPR) for amphetamine derivatives based on neighborhood degree-based topological indices and NM-polynomials. By coupling such descriptors to both polynomial regression models and Random Forest algorithms, the ability of these two methodologies to predict different physicochemical properties (boiling point, evaporation energy, flash point, molar refractivity, surface tension, polarizability and SA) is analyzed. The modeling scheme reveals that the neighborhood-based indices carry information specific to structural complexity, connectivity and electronic characteristics important for stimulant-type molecules behaviour. cubic regression models are also found to be more capable of representing nonlinear structural relationship than quadratic ones while the efficacy and generalizability are greatly improved by extra Random Forest in particular for properties with strong dependence on molecular branching and electronic distribution. In conclusion, the results here presented confirm that NM-polynomial based descriptors effectively relate molecular topology with experimentally measurable physicochemical behavior, thus suggesting their computational use in predictive property modeling, early drug screening and cheminformatics-driven design.