Development of a displacer-immobilized ligand docking scheme for displacer screening for protein displacement chromatography

Displacement chromatography is a powerful technique for protein purification, but the availability of high-efficacy displacers has greatly limited its applications. In this work, a displacer-immobilized ligand docking scheme was developed for the prediction of displacer efficacy and displacer screening for displacement chromatography of proteins. The structure of immobilized ligand was established by coupling a certain number of ligands to the 3D structure of agarose. A number of known cation, anion and hydrophobic displacers were docked to their respective immobilized ligands to verify the effectiveness of the scheme, and the Spearman ranking correlation coefficients of all cases were over 0.5. The scheme was then used to screen displacers for hydrophobic charge induction chromatography from over 1800 commercially available compounds. Column displacement experiments of several representative compounds showed that the identified displacers were efficacious in the displacement of single component and binary mixtures. It is expected that the combination of the docking scheme with the existing techniques for displacer discovery/design would greatly facilitate the discovery of high-affinity displacers for protein purification.

► A displacer-immobilized ligand docking scheme was developed for the prediction of displacer efficacy in protein displacement chromatography.
► The scheme was used to screen displacers for hydrophobic charge induction chromatography.
► Column displacement experiments showed that the identified displacers are efficacious.
► Combination of the docking scheme with existing techniques would greatly facilitate the discovery of high-affinity displacers for protein purification.