The pharmacophore concept is a fundamental cornerstone in drug discovery, playing a critical role in determining the success of in silico techniques, such as virtual screening and 3D-QSAR studies. The reliability of these approaches is influenced by the quality of the physicochemical descriptors used to characterize the chemical entities. In this context, a pivotal role is exerted by lipophilicity, which is a major contribution to host-guest interaction and ligand binding affinity. Several approaches have been undertaken to account for the descriptive and predictive capabilities of lipophilicity in 3D-QSAR modeling. Recent efforts encode the use of quantum mechanical-based descriptors derived from continuum solvation models, which open novel avenues for gaining insight into structure-activity relationships studies.
Keywords: 3D-QSAR; continuum solvation models; hydrophobic pharmacophore; lipophilicity; quantum mechanical-derived descriptors.