| Abstract
| - It has been shown that the rate-limiting step in the production of β-amyloid peptide (Aβ) isthe proteolytric cleavage of the membrane-bound β-amyloid precursor protein (APP) byβ-secretase (BACE). Since the accumulation of Aβ has been implicated as one of the key eventsin the progression of Alzheimer's disease, BACE has become an important therapeutic target.Recently, two crystal structures of BACE cocrystallized with the inhibitors OM99-2 and OM00-3were published by Tang and co-workers. In addition, the Ghosh group has published bindingdata on a series of inhibitors based on their initial lead, OM99-2. Using this set as a basis, wehave developed a model for the binding affinity of these ligands to BACE using the linearinteraction energy method. The best binding affinity model for the full set of ligands had aRMSD of 1.10 kcal/mol. The best model excluding the two charged ligands had a RMSD of0.87 kcal/mol.
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