Predictions of the interaction between Triazaspiro and BACE1 enzyme

The search for compounds capable of inhibiting the BACE1 that constitutes one of the pharmacological targets used to reduce the levels of amyloid precursor protein, which are increased in people with Alzheimer’s disease. BACE1 is an aspartyl protease that cuts the of amyloid precursor protein. In this study analyzed different conformations of triazaspiro in the active site Beta-secretase. The individual analysis of each pose allowed us to visualize the interactions between these compounds and their coupling in the active site 3msj enzyme. Six ligands showed interactions with imidazolone ring, the methylene group and the nitrogen of the piperidine with amino acid residues in the beta-secretase: Trp-76, Gly-34, Arg-128 and Asp- 228, other ligands showing binding with: Ser-229, Gly-13, Gly-11 and Ala-335. In this preliminary study, we postulated two interaction sites between triazaspiro and BACE1. The variation of energies was -10,227 and -11.54 Kcal/mol in the two programs of docking.