A Molecular Dynamics Simulation of the Human Lysozyme -Camelid VHH HL6 Antibody System

Abstract

Amyloid diseases such as Alzheimer's and thrombosis are characterized by an aberrant assembly of specific proteins or protein fragments into fibrils and plaques that are deposited in various tissues and organs. The single-domain fragment of a camelid antibody was reported to be able to combat against wild-type human lysozyme for inhibiting in-vitro aggregations of the amyloidogenic variant (D67H). The present study is aimed at elucidating the unbinding mechanics between the D67H lysozyme and VHH HL6 antibody fragment by using steered molecular dynamics (SMD) simulations on a nanosecond scale with different pulling velocities. The results of the simulation indicated that stretching forces of more than two nano Newton (nN) were required to dissociate the protein-antibody system, and the hydrogen bond dissociation pathways were computed.