<i>In Silico</i> Analysis of Anthrax Antitoxin CMG2-Fc: Glycosylation, Linker Design, and Binding Ability

CMG2-Fc is a synthetic, chimeric glycoprotein that serves as an antitoxin for anthrax. It is a dimer, with one glycosylation site per monomer. A synthetic linker is used to join the CMG2 and Fc domains. Since the CMG2 and Fc domains bind separate cofactors (Anthrax's Protective Agent and immune receptor FcγRIIIA, respectively), the linker could play a significant roll in the binding ability of each domain. Additionally, the glycosylation sites are located in close proximity to the linker and can affect the association of the CMG2 and Fc domains. In this work, we investigate different linkers and glycosylation profiles for CMG2-Fc, and elucidate how these variables affect structure and function. We employ standard molecular dynamics to study the structure and dynamics of CMG2-Fc variants, and use the method of well-tempered metadynamics to study the binding of CMG2-Fc and its cofactors.