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

Int J Mol Sci. 2014 Mar 24;15(3):5128-39. doi: 10.3390/ijms15035128.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Amyloid Precursor Protein Secretases / chemistry
  • Amyloid Precursor Protein Secretases / metabolism
  • Binding Sites
  • Catalytic Domain
  • Computational Biology / methods*
  • Computer Simulation
  • Computer-Aided Design*
  • Crystallography, X-Ray
  • Drug Design*
  • Models, Molecular
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / metabolism
  • Protease Inhibitors / pharmacology*
  • Protein Binding
  • Protein Structure, Tertiary
  • Reproducibility of Results


  • Protease Inhibitors
  • Amyloid Precursor Protein Secretases