Molecular Dynamics and Molecular Docking Studies on the Interaction between Four Tetrahydroxy Derivatives of Polyphenyls and Beta Amyloid

Abstract

Interactions of 3,3',4,4'-tetrahydroxybiphenyl (BPT) and three isomeric 3,3",4,4"-tetrahydroxyterphenyls (OTT, MTT, PTT) with Alzheimer's amyloid-β peptide (Aβ) were studied by molecular dynamics simulation and molecular docking. Structural parameters such as Root-mean-square derivations (RMSD), radial distribution function (RDF), helix percentage and other physical parameters were obtained. These inhibitors have been evaluated and compared for their activity against aggregation of Aβ. The results showed that all four compounds successfully inhibit association of Aβ and reduce aggregation of protein. For the tetrahydroxyterphenyls efficacy varies with linker geometry: the <em>ortho</em>-position affords the most successful inhibition and the <em>para</em>-geometry the least perhaps due to differing abilities of these inhibitors to bind amyloid-β peptide. Of the four small inhibitors studied 3,3',4,4'-tetrahydroxybiphenyl (BPT) is the most effective inhibitor. Molecular docking studies have been done to confirm the simulation results. Investigation of binding site and free energy confirmed that the efficiency of interaction with Aβ depends on differing abilities of these inhibitors to bind amyloid-β peptide. Binding energy of BPT is more negative than the other and it significantly decreases for PTT. Self-aggregation of this inhibitor decreases in comparison with BPT; therefore Aβ aggregation in the presence of biphenyl form is higher than terphenyls.