title: Application of computational methods for the design of BACE-1 inhibitors: validation of in silico modelling.
abstract: β-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 β-secretase inhibitors could be widely used in the design process.
authors.affiliation: Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland. marek.bajda@chem.uw.edu.pl.
authors.forename: Marek
authors.initials: M
authors.lastname: Bajda
authors.affiliation: Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Cracow, Poland. jakub.jonczyk@uj.edu.pl.
authors.forename: Jakub
authors.initials: J
authors.lastname: Jończyk
authors.affiliation: Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Cracow, Poland. barbara.malawska@uj.edu.pl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Malawska
authors.affiliation: Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland. sfilipek@chem.uw.edu.pl.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Filipek
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D017076:Computer-Aided Design; D018360:Crystallography, X-Ray; D015195:Drug Design; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results
chemical_list: D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases