The atom assignment problem in automated de novo drug design. 5. Tests for envelope-directed fragment placement based on molecular similarity.

The fragment placement method has been successfully extended to the problem of envelope-directed design. The atom assignment paradigm was based on molecular similarity between two molecular structures. A composite supersurface is defined to form the surface onto which the molecular fields are projected. The assignment process is then determined by using molecular similarity in the objective function to be optimized. In principle, this procedure is closely similar to that outlined in the previous paper for site-directed design. The rationale has been extensively tested on two benzodiazepine antagonists believed to bind to the same site.