Ontology highlight
ABSTRACT:
SUBMITTER: Ellis CR
PROVIDER: S-EPMC5713896 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
Ellis Christopher R CR Tsai Cheng-Chieh CC Hou Xinjun X Shen Jana J
The journal of physical chemistry letters 20160225 6
Targeting β-secretase (BACE1) with small-molecule inhibitors offers a promising route for treatment of Alzheimer's disease. However, the intricate pH dependence of BACE1 function and inhibitor efficacy has posed major challenges for structure-based drug design. Here we investigate two structurally similar BACE1 inhibitors that have dramatically different inhibitory activity using continuous constant pH molecular dynamics (CpHMD). At high pH, both inhibitors are stably bound to BACE1; however, wi ...[more]