Publications (2)9.53 Total impact
-
Article: Computational Methods in the Discovery and Design of BACE-1 Inhibitors.
[show abstract] [hide abstract]
ABSTRACT: BACE-1 is a membrane associated aspartyl protease and is one of the enzymes responsible for the hydrolysis of the amyloid precursor protein. Due to its central role in the generation of the amyloid-β peptide, it is considered as a primary drug target for Alzheimer's disease. BACE-1 has been the focus of many drug discovery programs aimed at identifying inhibitors that effectively block this enzyme and trigger the sought therapeutic effects. Thanks to the availability of a large number of crystal structures of the catalytic domain of this enzyme, computational methods, ranging from molecular dynamics simulations, quantum mechanical calculations and ligand docking, have played a fundamental role in almost every hit discovery and hit optimization campaign performed on this target. The present article reviews the latest computational modeling and drug discovery efforts that have been carried out on this target.Current Medicinal Chemistry 10/2012; · 4.86 Impact Factor -
Article: Combining dyad protonation and active site plasticity in BACE-1 structure-based drug design.
[show abstract] [hide abstract]
ABSTRACT: The ability of the BACE-1 catalytic dyad to adopt multiple protonation states and the conformational flexibility of the active site have hampered the reliability of computational screening campaigns carried out on this drug target for Alzheimer's disease. Here, we propose a protocol that, for the first time, combining quantum mechanical calculations, molecular dynamics, and conformational ensemble virtual ligand screening addresses these issues simultaneously. The encouraging results prefigure this approach as a valuable tool for future drug discovery campaigns.Journal of Chemical Information and Modeling 02/2012; 52(5):1079-85. · 4.68 Impact Factor
Top co-authors
Top Journals
Institutions
-
2012
-
Italian Institute of Technology (IIT)
- Department of Drug Discovery and Development
Genova, Liguria, Italy
-
