STUDY OF THE INFLUENCE OF THE STRUCTURE OF THE MOLECULE ON ITS ABILITY TO SELECTIVELY INHIBIT BACE1

Abstract

Computer modeling of potential inhibitors of hBACE1 in relation to ADAM10 and γ-secretase was carried out. The influence of the basicity of the ligand molecule and the presence of a trifluoromethyl group in the aromatic ring the affinity energy and selectivity of individual members of the protease membrane complex consisting of hBACE1, ADAM10 and γ-secretase was studied. The influence of the molecular weight of the ligand on the affinity energy was studied as well. A number of potentially the most selective compounds that form stronger complexes with hBACE1, selectively inhibiting hBACE1 in the enzymatic membrane complex, compared to the original ligand, were identified