AB-INITIO ELECTRONIC-STRUCTURE CALCULATIONS OF MOLECULAR SIMILARITY -A CASE-STUDY OF 4-AMINOBUTYRIC ACID AND ITS AGONISTS

A new quantum mechanical measure of molecular similarity, based on the overlap between the first-order density matrices is applied in studie s of the structure-activity relationships in the GABA(A) agonists: tra ns-4-amino-crotonic acid, 5-aminomethylisoxazol-3-ol, and 3-aminomethy lisoxazol-5-ol. The geometries of these molecules are optimized at the HF/6-31G level and their electronic structures compared to that of 4- aminobutyric acid. Factors affecting the GABAergic activity of these s ubstances are discussed. The present study demonstrates that ab initio electronic structure calculations of molecular similarity are feasibl e for medium-sized molecules of biological interest.