Computational quantum chemistry and adaptive ligand modeling in mechanistic QSAR

Drugs are adaptive molecules. They realize this peculiarity by generating different ensembles of prototropic forms and conformers that depend on the environment. Among the impressive amount of available computational drug discovery technologies, quantitative structure–activity relationship approaches that rely on computational quantum chemistry descriptors are the most appropriate to model adaptive drugs. Indeed, computational quantum chemistry descriptors are able to account for the variation of the intramolecular interactions of the training compounds, which reflect their adaptive intermolecular interaction propensities. This enables the development of causative, interpretive and reasonably predictive quantitative structure–activity relationship models, and, hence, sound chemical information finalized to drug design and discovery.