Modelling of lysozyme binding to a cation exchange surface at atomic detail: the role of flexibility.

Different approaches were made to predict the adsorbed orientation based on rigid, flexible, or a mixture of both models. To determine the role of flexibility during adsorption, the orientation of lysozyme adsorbed to a negatively charged ligand surface was predicted by a rigid and a flexible model based on two differing protein structures at atomic resolution. For the rigid model, the protein structures were placed at different distances from the ligand surface and the electrostatic interaction energy was calculated for all possible orientations. The results were compared to a flexible model where the binding to the ligand surface was modeled by multiple molecular dynamics simulations starting with 14 initial orientations. Different aspects of the adsorption process were not covered by the rigid model and only detectable by the flexible model. Whereas the results of the rigid model depended sensitively on the protein-surface distance and the protein structure, the preferred orientation obtained by the flexible model was closer to a previous experimental determined orientation, robust toward the initial orientation and independent of the initial protein structure. Additionally, it was possible to obtain insights into the preferred binding process of lysozyme on a negatively charged surface by the flexible model.