Structure modeling and hybrid virtual screening study of Alzheimer’s associated protease kallikrein 8 for the identification of novel inhibitors

Kallikrein 8 (KLK8) is an extra cellular serine protease which is responsible for nerve growth, and degeneration and nervous plasticity have been associated with Alzheimer’s disease. In silico analysis of KLK8 has not been performed until now. This study is aimed at molecular modeling and lead identification for a potent inhibitor. The hybrid of ligand- and structure-based virtual screening was applied on commercially available compounds. Ligand similarity search was employed, followed by ligand docking protocol. Compound’s potential for their activity was deduced from docking scores and their interactions with the active site. For active permeation of compounds through blood brain barrier, their molecular properties were checked with previously reported compounds. The compound that showed the most potential according to criteria was 1-(3,5-difluorophenyl)-5-hydroxy-7-(4-hydroxy-3,5-dimethoxyphenyl)-6,7-dihydro-1H-pyrrolo[3,2-b] pyridine-3-carboxylic acid (ZINC 61720639).