Molecular Insight into
the Ligand–IgG
Interactions for 4-Mercaptoethyl-pyridine Based Hydrophobic Charge-Induction
Chromatography
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Abstract
Hydrophobic charge-induction chromatography (HCIC) with
4-mercaptoethyl-pyridine
(MEP) as the ligand is a novel technology for antibody purification.
In the present work, the molecular simulation methods were used to
investigate the interactions between MEP ligand and Fc fragment of
IgG (Fc-A). Six ligands with different structures of spacer arm were
studied with molecular docking and dynamics simulation at neutral
and acidic pH. The binding modes and the interaction energies were
analyzed. The results indicated that all ligands tested could bind
into the selected pocket on the C<sub>H2</sub> domain of Fc-A at neutral
pH. The pyridine ring on the top of MEP ligands acts as a major role
to provide the hydrophobic association and hydrogen bond for the ligand–IgG
binding; meanwhile, the sulfone group on the spacer arm might form
the additional hydrogen bond and enhance the binding of ligand onto
the surface of IgG. The replacements of thioether sulfur atom on the
spacer arm with either nitrogen or oxygen atom seem to have little
influence on the binding. The influences of pH on the ligand–IgG
interactions were also studied with the molecular dynamics simulation.
It was found that MEP ligands would departed from the surface of Fc-A
at low pH due to the electrostatic repulsion. The ligands with a sulfone
group on the spacer arm would weaken the electrostatic repulsion and
need more acidic conditions for the departing of ligand. The molecular
simulation results were in agreement with some experimental observations,
which would be useful to elucidate the molecular mechanism of HCIC
and design a novel ligand to improve the efficiency of antibody separation