Chirality Descriptors for Structure–activity Relationship Modeling of Bioactive Molecules

Owing to the homochirality among the α-amino acids, the building blocks, chiral environmental prevails within the structure of biological macromolecules namely, the proteins, receptors, and enzymes. This results in chiral distinction of the ligands such as drug molecules and toxicants by the biological targets. Chiral distinction of enantiomers is not only important in the biological activity of enantiomers but also in pharmacokinetics and metabolism of chemicals. The molecular descriptors that are based only on the connectivity of atoms cannot differentiate the enantiomers and diastereomers. In order to model the differential activity of enantiomers and diastereomers, molecular descriptors capable of encoding the difference in spatial arrangements of atoms and groups around a chiral center are needed. In this paper we report a modified approach that enables to compute a large pool of chirality descriptors for a given set of molecules. The new chirality descriptors can differentiate enantiomers and diastereomers. Application of the new chiral descriptors in structure–activity modelling of bioactivity of chiral molecules is illustrated for the dopamine (DA) D2 and opiate σ receptor affinities of seven pairs of enantiomers of 3-(3-hydroxyphenyl)piperidines.