Application of computational methods for the design of BACE-1 inhibitors: validation of in silico modelling.

ABSTRACT: ?-Secretase (BACE-1) constitutes an important target for search of anti-Alzheimer's drugs. The first inhibitors of this enzyme were peptidic compounds with high molecular weight and low bioavailability. Therefore, the search for new efficient non-peptidic inhibitors has been undertaken by many scientific groups. We started our work from the development of in silico methodology for the design of novel BACE-1 ligands. It was validated on the basis of crystal structures of complexes with inhibitors, redocking, cross-docking and training/test sets of reference ligands. The presented procedure of assessment of the novel compounds as ?-secretase inhibitors could be widely used in the design process.

SUBMITTER: Bajda M 

PROVIDER: S-EPMC3975444 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature