title: A comprehensive molecular dynamics approach to protein retention modeling in ion exchange chromatography.
abstract: 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.
authors.affiliation: Section IV: Biomolecular Separation Engineering, Institute of Process Engineering in Life Sciences, Karlsruhe Institute of Technology (KIT), Engler-Bunte-Ring 1, 76131 Karlsruhe, Germany.
authors.forename: Katharina M H
authors.initials: KM
authors.lastname: Lang
authors.affiliation: Section IV: Biomolecular Separation Engineering, Institute of Process Engineering in Life Sciences, Karlsruhe Institute of Technology (KIT), Engler-Bunte-Ring 1, 76131 Karlsruhe, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kittelmann
authors.affiliation: Section IV: Biomolecular Separation Engineering, Institute of Process Engineering in Life Sciences, Karlsruhe Institute of Technology (KIT), Engler-Bunte-Ring 1, 76131 Karlsruhe, Germany.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Dürr
authors.affiliation: Section IV: Biomolecular Separation Engineering, Institute of Process Engineering in Life Sciences, Karlsruhe Institute of Technology (KIT), Engler-Bunte-Ring 1, 76131 Karlsruhe, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Osberghaus
authors.affiliation: Section IV: Biomolecular Separation Engineering, Institute of Process Engineering in Life Sciences, Karlsruhe Institute of Technology (KIT), Engler-Bunte-Ring 1, 76131 Karlsruhe, Germany. Electronic address: juergen.hubbuch@kit.edu.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hubbuch
mesh_terms: D000327:Adsorption; D001120:Arginine / Q000737:chemistry; D001224:Aspartic Acid / Q000737:chemistry; D002852:Chromatography, Ion Exchange / Q000379:methods; D018698:Glutamic Acid / Q000737:chemistry; D007768:Lactalbumin / Q000737:chemistry; D008027:Light; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D054467:Phospholipases A2 / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D012259:Ribonuclease, Pancreatic / Q000737:chemistry; D012542:Scattering, Radiation; D012685:Sepharose / Q000737:chemistry
chemical_list: D011506:Proteins; D001224:Aspartic Acid; D018698:Glutamic Acid; D012685:Sepharose; D007768:Lactalbumin; D001120:Arginine; D054467:Phospholipases A2; D012259:Ribonuclease, Pancreatic
keywords: Ion exchange chromatography; Molecular dynamics simulation; Molecular models; Non-standard residues; PDB preprocessing; Retention model