Computer based screening of compound databases: 1. Preselection of benzamidine-based thrombin inhibitors

We present a computational protocol which uses the known three-dimensional structure of a target enzyme to identify possible ligands from databases of compounds with low molecular weight. This is accomplished by first mapping the essential interactions in the binding site with the program GRID. The resulting regions of favorable interaction between target and ligand are tr anslated into a database query, and with UNITY a flexible 3D database searc h is performed. The feasibility of this approach is calibrated with thrombi n as the target. Our results show that the resulting hit lists are enriched with thrombin inhibitors compared to the total database.