Fc-binding proteins and ligands play an important role in the antibody downstream processing.  Reversible yet strong binding affinity between Fc on antibodies and proteins or ligands is critical for antibody purification based on affinity chromatography. Consensus Binding Site (CBS) region is a well-studied binding site on the Fc fragment. Protein A and Protein G have been well investigated and found to bind with Fc fragment at CBS region. Recently, our earlier investigations screened and selected seven novel high affinity Fc-binding heptapeptides from a combinatorial peptide library using phage display and ELISA. In this work, protein-ligand docking and molecular dynamics (MD) simulations were carried out to investigate the binding mechanism of these novel Fc-binding heptapeptides. A new binding region rather than CBS on Fc fragment was found, which located at the center of Fc fragment around the glycan residues. The binding mechanism was elucidated. Moreover, Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) method was used to calculate the binding free energies. A very good agreement was obtained between theory and experiments.

Molecular recognition of novel heptapeptides at Fc-binding sites from molecular dynamics simulations

251st National Meeting (2016)

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