Molecular modelling of GABA uptake inhibitors

Abstract

A joint molecular modelling and computer graphics study of the potent and conformatio-nally flexible GABA uptake inhibitor SKF 89.976-A is presented. Two principally different approaches for determining the biologically active conformation(s) are described. In the first approach, three flexible compounds are compared in order to find differences between the potent SKF compound, an inactive and a less active compound. In the second approach, SKF 89.976-A is compared with a conformationally constrained GABA uptake inhibitor. The results are compared and a tentative model for the recognition site deduced.

Key Words:

• omputer graphics
• GABA uptake inhibitors
• Molecular modelling