| Title : Identification of novel Acetylcholinesterase inhibitors through e-pharmacophore based virtual screening and molecular dynamics simulations - Malik_2017_J.Biomol.Struct.Dyn_35_3268 |
| Author(s) : Malik R , Choudhary BS , Srivastava S , Mehta P , Sharma M |
| Ref : J Biomol Struct Dyn , :1 , 2016 |
|
Abstract :
Alzheimer's disease (AD), a progressive neurodegenerative disorder is the most common cause of dementia among elderly people. To date, the successful therapeutic strategy to treat AD is maintaining the levels of acetylcholine via inhibiting acetylcholinesterase (AChE). The present study involves identification of newer AChE inhibitors by dual approach of e-pharmacophore and structure based virtual screening of Asinex library. Robustness of docking protocol was validated by enrichment calculation with ROC value 0.71 and BEDROC value 0.028. Among eleven selected hits, ZINC72338524 with best MM-GBSA dG binding shows optimal range of CNS properties and ligand-AChE complex stability. Further, molecular dynamics study revealed its molecular interactions with Trp86, Phe338 and Tyr341 amino acid residues of catalytic anionic site and Tyr124, Ser125 and Trp286 amino acid residues of peripheral anionic site. Physicochemical properties and ADMET risk prediction indicates their potential in druggability and safety. |
| PubMedSearch : Malik_2017_J.Biomol.Struct.Dyn_35_3268 |
| PubMedID: 27782777 |
Malik R, Choudhary BS, Srivastava S, Mehta P, Sharma M (2016)
Identification of novel Acetylcholinesterase inhibitors through e-pharmacophore based virtual screening and molecular dynamics simulations
J Biomol Struct Dyn
:1
Malik R, Choudhary BS, Srivastava S, Mehta P, Sharma M (2016)
J Biomol Struct Dyn
:1