COMP 57 |
| Fragment based drug discovery has become a hot topic in recent years. The eHiTS docking program has been using a fragment based approach to docking since its inception. The algorithm divides input molecules into fragments and docks each fragment independently of the others before reconnecting to re-form the input molecule. Applying this methodology to fragment based de novo ligand design is a natural extension resulting in an efficient new tool. BACE-1 is a well studied flexible enzyme with implications in the treatment of Alzheimer's disease and over 30 public crystal structures. Using a set of co-crystallized ligands, we fragment the ligands and dock the fragments. By comparing the fragment poses to the original ligand pose, we can validate the ability of this protocol to reproduce known binders from fragments. It will be demonstrated how fragment docking results from various known ligands can be recombined and linked with additional common fragments to form some novel potential BACE-1 inhibitors. |
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Drug Discovery
8:00 AM-11:35 AM, Monday, April 7, 2008 Morial Convention Center -- Rm. 348, Oral
Division of Computers in Chemistry |