A comprehensive molecular dynamics approach to protein retention modeling in ion exchange chromatography

•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.•Interaction areas on cation exchangers are defined by arginines.•Interaction areas on anion exchangers are defined by aspartic acids. In downstream processing, the underlying adsorption mechanism of biomolecules to adsorbent material are still subject of extensive research. One approach to more mechanistic understanding is simulating this adsorption process and hereby the possibility to identify the parameters with strongest impact. So far this method was applied with all-atom molecular dynamics simulations of two model proteins on one cation exchanger. In this work we developed a molecular dynamics tool to simulate protein–adsorber interaction for various proteins on an anion exchanger and ran gradient elution experiments to relate the simulation results to experimental data. We were able to show that simulation results yield similar results as experimental data regarding retention behavior as well as binding orientation. We could identify arginines in case of cation exchangers and aspartic acids in case of anion exchangers as major contributors to binding.