Evaluating scoring functions for docking and designing beta-secretase inhibitors.
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.
Katharine Holloway
M
M
Department of Molecular Systems, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. kate_ holloway@merck.com
McGaughey
Georgia B
GB
Coburn
Craig A
CA
Stachel
Shawn J
SJ
Jones
Kristen G
KG
Stanton
Elizabeth L
EL
Gregro
Alison R
AR
Lai
Ming-Tain
MT
Crouthamel
Ming-Chih
MC
Pietrak
Beth L
BL
Munshi
Sanjeev K
SK
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
D004791:Enzyme Inhibitors; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human