Molecular docking and quantum mechanical studies on biflavonoid structures as BACE-1 inhibitors

Abstract

Beta-site amyloid precursor protein cleaving enzyme (BACE-1) is a well-known therapeutic target for Alzheimer disease (AD) due to its characteristic role in the pathogenesis of AD. Numerous researches have been focused on the design and development of potent peptidic and nonpeptidic BACE-1 inhibitors. In the present contribution, a series of experimentally validated biflavonoid BACE-1 inhibitors (1-21) were subjected to our structure-based molecular modeling studies. Binding modes were elucidated through molecular docking in the active site of the enzyme. Relatively good correlations between the theoretical and experimental binding affinities could be achieved (R 2 = 0.61). Analysis of intermolecular binding energy components was performed via functional B3LYP in association with splitvalence basis set using polarization functions (Def2-SVP), and structure-binding relationships were further elucidated through ligand-residue binding energies. Since little studies have been performed on the modeling and structure activity/binding relationships of biflavonoid structures as BACE-1 inhibitors, the results of this study may be useful in further extending the scope of biflavonoid structures as potential anti-Alzheimer scaffolds.

Synthesis of Biuret Derivatives as Potential HIV‐1 Protease Inhibitors Using (LDHs‐g‐HMDI‐Citric Acid), as a Green Recyclable Catalyst

“…As shown in Figure 8, the biuret moiety in the majority of the selected compounds participates in hydrogen bonding with Asp 25, Gly 27, and Ile 50. The hydrogen bonding of Asp 25 with different inhibitors has been previously reported 67 . In summary, docking results revealed that all of the selected compounds could occupy an HIV‐1 protease active site.…”

“…The HIV‐1 protease is a homodimeric protease including two identical 99‐residue monomers. Each monomer consists of the conserved triads (Asp‐Thr‐Gly) in positions of 25–27 and 25′–27′, that aspartate amino acids do all of the catalytic activities 67 . All the selected compounds were successfully docked into the corresponding active site of HIV‐1 protease (Figure 8).…”

Simulational and theoretical study of electron scattering cross section by Chlormethine-DNA complex

“…Maximum generation was set as 27 000 with 5 000 000 number of energy evaluations in 200 genetic algorithm runs, 0.02 and 0.8 for gene mutation rate and crossover rate respectively. Final cluster analysis of similar conformations was applied with the root mean square deviation (RMSD) tolerance of 2 [12]. Different conformers with total number of 150 were produced following the genetic algorithm.…”

Interplay of thermochemistry and Structural Chemistry, the journal (Volume 26, 2015, Issues 1–2) and the discipline

“…Razzaghi-Asl et al [143] reported the results of a theoretical structure-based molecular modeling study of a therapeutic target for Alzheimer's disease, a beta-site amyloid precursor protein-cleaving enzyme, which was previously experimentally validated. A reasonable correlation (R 2 = 0.61) was calculated between the theoretical and experimental binding affinities.…”