Application of Computational Methods for the Design of BACE-1 Inhibitors: Validation of in Silico Modelling |
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Authors: | Marek Bajda Jakub Jończyk Barbara Malawska S?awomir Filipek |
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Affiliation: | 1.Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland; E-Mail: ;2.Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Cracow, Poland; E-Mails: (J.J.); (B.M.) |
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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. |
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Keywords: | β -secretase BACE-1 inhibitor molecular modelling docking studies validation |
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