Multimodal (MM) chromatography offers unique opportunities for bioseparations because of the presence of multiple aspects of protein-ligand interactions which can be manipulated to achieve desired selectivities. The key components in these MM chromatographic systems include proteins, ligands, water and co-solutes. In the present study, we focus on the use of fluid phase modifiers and temperature to modulate the interactions between proteins and MM ligands in the presence of water. All-atom molecular dynamics (MD) simulations were employed to gain mechanistic insights into the effects of urea, arginine and guanidinium chloride on MM ligand-protein binding. The effect of temperature on the multiple modes of interactions, especially hydrophobic interactions, was also studied. Combined with experimental results obtained from chromatography and Nuclear Magnetic Resonance (NMR) spectroscopy, this fundamental study can be used to develop tools for characterization of MM ligand-protein interactions to accelerate downstream process development.

Mobile phase modifier and temperature effects in multimodal chromatography: Insights from molecular dynamics simulations

245th National Meeting (2013)

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