Identification Mechanism of BACE1 on Inhibitors Probed by Using Multiple Separate Molecular Dynamics Simulations and Comparative Calculations of Binding Free Energies.

ABSTRACT: β-amyloid cleaving enzyme 1 (BACE1) is regarded as an important target of drug design toward the treatment of Alzheimer's disease (AD). In this study, three separate molecular dynamics (MD) simulations and calculations of binding free energies were carried out to comparatively determine the identification mechanism of BACE1 for three inhibitors, 60W, 954 and 60X. The analyses of MD trajectories indicated that the presence of three inhibitors influences the structural stability, flexibility and internal dynamics of BACE1. Binding free energies calculated by using solvated interaction energy (SIE) and molecular mechanics generalized Born surface area (MM-GBSA) methods reveal that the hydrophobic interactions provide decisive forces for inhibitor-BACE1 binding. The calculations of residue-bas

SUBMITTER: Wang Y 

PROVIDER: S-EPMC10305653 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature