Custom-tailored adsorbers: A molecular dynamics study on optimal design of ion exchange chromatography material

• We developed a predictive molecular dynamics (MD) tool for interaction simulations.
• The MD tool can handle non-standard residues in biomolecules.
• The MD tool is capable of predicting interactions and retention behavior.
• Ionic capacities could be depicted successfully in simulations.
• Simulations can be used as pre-experimental screening for adsorber optimization.

The performance of functionalized materials, e.g., ion exchange resins, depends on multiple resin characteristics, such as type of ligand, ligand density, the pore accessibility for a molecule, and backbone characteristics. Therefore, the screening and identification process for optimal resin characteristics for separation is very time and material consuming. Previous studies on the influence of resin characteristics have focused on an experimental approach and to a lesser extent on the mechanistic understanding of the adsorption mechanism. In this in silico study, a previously developed molecular dynamics (MD) tool is used, which simulates any given biomolecule on resins with varying ligand densities. We describe a set of simulations and experiments with four proteins and six resins varying in ligand density, and show that simulations and experiments correlate well in a wide range of ligand density. With this new approach simulations can be used as pre-experimental screening for optimal adsorber characteristics, reducing the actual number of screening experiments, which results in a faster and more knowledge-based development of custom-tailored adsorbers.