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 β-amyloid peptide (Aβ) 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 Aβ, the binding modes between Aβ1-42 and the envelop glycoprotein D (gD) of Herpes simplex virus-1 (HSV-1)/Aβ1-42 were theoretically investigated by using molecular docking, molecular dynamics (MD) simulations and binding free energy decomposition methods in the present study. The Aβ1-42 stably binds to the envelop gD via intermolecular hydrogen bonds and van der Waals (vdW) interactions. The Aβ1-42 acquires its equilibrium with higher fluctuation amplitude and a better structured C-terminal in the HSV-1 gD–Aβ1-42 complex comparing to that in the Aβ1-42–Aβ1-42 complex. The amino acid residues of Aβ1-42 involved in the formation of the Aβ1-42 dimer are fully free and accessible in the HSV-1 gD–Aβ1-42 complex. It is favorable for the Aβ1-42 monomer to interact with the HSV-1 gD–Aβ1-42 complex. It may be responsible for the rapid amyloidosis which entraps the herpesvirus as well as causing AD. [Display omitted] •Human herpesvirus infection is linked to Alzheimer's disease (AD) due to the protective role of Aβ in the central nervous system (CNS).•Aβ1-42 is able to target on the surface of Herpes simplex virus-1 (HSV-1) through binding to the glycoprotein D (gD) stably with intermolecular hydrogen bonds and van der Waals interactions.•The Aβ1-42 acquires its equilibrium with higher fluctuation amplitude and a better structured C-terminal in the HSV-1 gD–Aβ1-42 complex comparing to that in the Aβ1-42–Aβ1-42 complex.•The amino acid residues of Aβ1-42 contributing to the formation of Aβ1-42 dimer are fully free and accessible in the HSV-1 gD–Aβ1-42 complex. It is favorable for the Aβ1-42 monomer to interact with the HSV-1 gD–Aβ1-42 complex and cause rapid amyloidosis.•The rapid amyloidosis is responsible for entrapping the herpesvirus as well as being associated with AD.