Molecular docking and molecular dynamics simulations studies on the protective and pathogenic roles of the amyloid-ß peptide between herpesvirus infection and Alzheimer's disease.

The protective innate immune response of ß-amyloid peptide (Aß) has been indicated as a risk factor for Alzheimer's disease (AD) due to the rapid amyloidosis. In order to obtain molecular-level insights into the protective and pathogenic roles of Aß, the binding modes between Aß1-42 and the envelop glycoprotein D (gD) of Herpes simplex virus-1 (HSV-1)/Aß1-42 were theoretically investigated by using molecular docking, molecular dynamics (MD) simulations and binding free energy decomposition methods in the present study. The Aß1-42 stably binds to the envelop gD via intermolecular hydrogen bonds and van der Waals (vdW) interactions. The Aß1-42 acquires its equilibrium with higher fluctuation amplitude and a better structured C-terminal in the HSV-1 gD-Aß1-42 complex comparing to that in the Aß1-42-Aß1-42 complex. The amino acid residues of Aß1-42 involved in the formation of the Aß1-42 dimer are fully free and accessible in the HSV-1 gD-Aß1-42 complex. It is favorable for the Aß1-42 monomer to interact with the HSV-1 gD-Aß1-42 complex. It may be responsible for the rapid amyloidosis which entraps the herpesvirus as well as causing AD.