Structure-activity relationships three-dimensional-ligand-based

Wurtz, J. M., Egner, U., Heinrich. N., Moras, D., Mueller-Fahrnow, A. Three-Dimensional Models of Estrogen Receptor Ligand Binding Domain Complexes, Based on Related Crystal Structures and Mutational and Structure-Activity Relationships Data,/. Med. Chem. 1998, 41, 1803-1814. 

The molecular basis for the left- and right-handedness of distinct crystals of the same chemical substance and the associated differences in optical rotation was developed from the hypothesis of Paterno (1869) and Kekule that the geometry about a carbon atom bound to four ligands is tetrahedral. Based on the concept of tetrahedral geometry, Van t Hoff and LeBel concluded that when four different groups or atoms are bound to a carbon atom, two distinct tetrahedral molecular forms are possible, and these bear a non-superimposable mirror-image relationship to one another (Fig. 3). This hypothesis provided the link between three-dimensional molecular structure and optical activity, and as such represents the foundation of stereoisomerism and stereochemistry. 

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