An alignment independent 3D-QSAR study for predicting the stability constants of structurally diverse compounds with β-cyclodextrin

Abstract

For the first time, to our opinion, an alignment free, three dimensional quantitative structure activity relationships (3D-QSAR) of stability constants of a large and heterogeneous variety of organic substances with β-cyclodextrin was reported. GRIND methodology, where descriptors are derived from GRID molecular interaction fields (MIF), was used. After variable selection via fractional factorial design (FFD), PLS analysis was carried out, and a highly descriptive and predictive model was obtained. The model satisfied a set of rigorous validation criteria and performed well in the prediction of an external test set. The proposed model is also checked for free from chance correlation, reliability and robustness by permutation testing called progressive y scrambling. The obtained models confirmed that size and shape of the molecules as well as hydrophobic interactions are the main parameters influencing the stabilities of diverse compounds—β-cyclodextrin inclusion complexes.