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

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