Quantum chemical approach to the relationship between molecular structure and serotonin receptor binding affinity

We have analyzed the dependence of the serotonin receptor binding affinity on the atomic net charges, superdelocalizabilities, mass, and moment of inertia in a group of indole derivatives. The approaches employed are a new nonempirical quantitative structure-activity relationship (QSAR) method and multiple regression analyses. The results suggest that the indole derivatives interact with the receptor through a charge transfer between the phenyl ring and a counterpart in the receptor, plus some localized electrostatic interactions. Also, the fit of the equation obtained suggests that the indole derivatives have the aromatic ring placed in the same relative position during the interaction with the receptor.