Modeling the binding affinities of beta-secretase inhibitors: application to subsite specificity.
A new linear binding affinity model has been developed for hydroxyethylene based inhibitors of beta-secretase (BACE). This model is an improvement over a previously published model, and has been applied to a series of analogs not included in the training set. The linear model has been used to study subsite specificity for the P(2) through P(2)' positions, and to evaluate a small number of C-terminal analogs. The predicted rankings are in good agreement with experiment and support using this model for structure-based design of BACE inhibitors.
Rajamani
Ramkumar
R
Johnson & Johnson Pharmaceutical Research and Development, Welsh and McKean Roads, PO Box 776, Spring House, PA 19477-0776, USA.
Reynolds
Charles H
CH
D053829:Amyloid Precursor Protein Secretases; D001665:Binding Sites; D015195:Drug Design; D010450:Endopeptidases / Q000737:chemistry* / Q000187:drug effects; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases