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

Interactions of 3,3#039 ,4,4#039 tetrahydroxybiphenyl (BPT) and three isomeric 3,3quot ,4,4quot tetrahydroxyterphenyls (OTT, MTT, PTT) with Alzheimer’s amyloidβ peptide (Aβ) were studied by molecular dynamics simulation and molecular docking. Structural parameters such as Rootmeansquare 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 orthoposition affords the most successful inhibition and the parageometry the least perhaps due to differing abilities of these inhibitors to bind amyloidβ peptide. Of the four small inhibitors studied 3,3#039 ,4,4#039 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 amyloidβ peptide. Binding energy of BPT is more negative than the other and it significantly decreases for PTT. Selfaggregation of this inhibitor decreases in comparison with BPT therefore Aβ aggregation in the presence of biphenyl form is higher than terphenyls.