title: Evaluating scoring functions for docking and designing beta-secretase inhibitors.
abstract: Several simple scoring methods were examined for 2 series of beta-secretase (BACE-1) inhibitors to identify a docking/scoring protocol which could be used to design BACE-1 inhibitors in a drug discovery program. Both the PLP1 score and MMFFs interaction energy (E(inter)) performed as well or better than more computationally intensive methods for a set of substrate-based inhibitors, while the latter performed well for both sets of inhibitors.
authors.affiliation: Department of Molecular Systems, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. kate_ holloway@merck.com
authors.forename: M
authors.initials: M
authors.lastname: Katharine Holloway
authors.forename: Georgia B
authors.initials: GB
authors.lastname: McGaughey
authors.forename: Craig A
authors.initials: CA
authors.lastname: Coburn
authors.forename: Shawn J
authors.initials: SJ
authors.lastname: Stachel
authors.forename: Kristen G
authors.initials: KG
authors.lastname: Jones
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Stanton
authors.forename: Alison R
authors.initials: AR
authors.lastname: Gregro
authors.forename: Ming-Tain
authors.initials: MT
authors.lastname: Lai
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Crouthamel
authors.forename: Beth L
authors.initials: BL
authors.lastname: Pietrak
authors.forename: Sanjeev K
authors.initials: SK
authors.lastname: Munshi
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation
chemical_list: D004791:Enzyme Inhibitors; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human