Adequate prediction for inhibitor affinity of Aβ₄₀ protofibril using the linear interaction energy method.

ABSTRACT: The search for efficient inhibitors targeting Aβ oligomers and fibrils is an important issue in Alzheimer's disease treatment. As a consequence, an accurate and computationally cheap approach to estimate the binding affinity for many ligands interacting with Aβ peptides is very important. Here, the calculated binding free energies of 30 ligands interacting with 12Aβ_11-40 peptides using the linear interaction energy (LIE) approach are found to be in good correlation with experimental data (R = 0.79). The binding affinities of these complexes are also calculated by using free energy perturbation (FEP) and molecular mechanic/Poisson-Boltzmann surface area (MM/PBSA) methods. The time-consuming FEP method provides results with similar correlation (R = 0.72), whereas MM/

SUBMITTER: Ngo ST 

PROVIDER: S-EPMC9063661 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature