Molecules, Vol. 28, Pages 8035: In Silico Design of Natural Inhibitors of ApoE4 from the Plant Moringa oleifera: Molecular Docking and Ab Initio Fragment Molecular Orbital Calculations

Molecules, Vol. 28, Pages 8035: In Silico Design of Natural Inhibitors of ApoE4 from the Plant Moringa oleifera: Molecular Docking and Ab Initio Fragment Molecular Orbital Calculations Molecules doi: 10.3390/molecules28248035 Authors: Divya Shaji Yoshinobu Nagura Haruna Sabishiro Ryo Suzuki Noriyuki Kurita Alzheimer’s disease (AD) is a neurological disease, and its signs and symptoms appear slowly over time. Although current Alzheimer’s disease treatments can alleviate symptoms, they cannot prevent the disease from progressing. To accurately diagnose and treat Alzheimer’s disease, it is therefore necessary to establish effective methods for diagnosis. Apolipoprotein E4 (ApoE4), the most frequent genetic risk factor for AD, is expressed in more than half of patients with AD, making it an attractive target for AD therapy. We used molecular docking simulations, classical molecular mechanics optimizations, and ab initio fragment molecular orbital (FMO) calculations to investigate the specific interactions between ApoE4 and the naturally occurring compounds found in the plant Moringa Oleifera. According to the FMO calculations, quercetin had the highest binding affinity to ApoE4 among the sixteen compounds because its hydroxyl groups generated strong hydrogen bonds with the ApoE4 residues Trp11, Asp12, Arg15, and Asp130. As a result, we proposed various quercetin derivatives by introducing a hydroxyl group into quercetin an...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research