Modification of Martini force field for molecular dynamics simulation of hydrophobic charge induction chromatography of lysozyme

Abstract

Modeling, especially the force field, is crucial for the accuracy of molecular dynamics (MD) simulations. In order for more accurate description of adsorption and desorption behaviors of lysozyme in hydrophobic charge induction chromatography (HCIC), the Martini coarse-grained (CG) force field has been modified based on the statistical analysis and comparison of an all-atom (AA) force field, GROMOS96 43A1, and the Martini force field. The parameters describing the protein–adsorbent interactions have been adjusted to avoid too strong and unrealistic adsorption of lysozyme on the agarose matrix and HCIC ligands. It is found that the adsorption and desorption behaviors monitored using the modified Martini force field and MD simulation are consistent with previous simulation results with 46-bead β-barrel model protein. Repeated adjustment of both protein position and orientation is necessary to generate enough contacts for a stable adsorption. After reducing the pH in the mobile phase, the lysozyme–ligand electrostatic repulsion leads to protein desorption. In the adsorption process, little conformational transition of lysozyme is observed due to its stable structure, which is in line with previous experimental observations. So, it is concluded that after appropriate modification, the Martini force field can be used to examine the HCIC process of lysozyme. The modification strategy has thus extended the applicability of the Martini force field to protein chromatography, and it is expected to facilitate studies of exploring the molecular details in adsorption chromatography of proteins.