Some new quantum chemical procedures for the analysis of drug—receptor interactions

The interaction of biologically active molecules with macromolecular receptors is analyzed in terms of preferred intermolecular orientation and the resulting intermolecular forces. The concept of an interaction pharmacophore representing a reactivity index for biologically active molecules and the representation of this pharmacophore by molecular electrostatic potentials are discussed and illustrated. A theoretical method for the analysis of multiple‐site interactions of large molecules is presented in terms of a double perturbation formalism. The method is applied to the model system of adenine interacting simultaneously with a molecule of water and an approaching proton. The results illustrate a possible mechanism for the preferential activation of secondary sites when a large molecule is already interacting at a primary reactive site.