Adsorption Orientation and Binding Motifs of Lysozyme and Chymotrypsin on Amorphous Silica

Abstract

The adsorption of α-chymotrypsin and hen egg white lysozyme on amorphous silica is studied by molecular dynamics (MD) simulations in comparison with adsorption experiments. Protein–surface interaction profiles are computed in implicit solvent at the level of DLVO theory. These reveal a preferential adsorption orientation for chymotrypsin, driven by its large dipole moment, with its α-helical regions pointing toward the surface. Instead, a less clear orientational preference characterizes lysozyme adsorption, which approaches the surface in a side-on orientation, confirming previous results. Explicit-solvent MD simulations are then performed to analyze the formation and stability of protein–surface contacts. While no significant conformational changes take place in the short simulation time investigated (up to 300 ns), the simulations clearly reveal the presence of adsorption motifs comprising both positively charged, but also negatively charged, polar and even nonpolar residues. Stable adsorption originates from a favorable match between the adsorption motifs and the local subnanometer distribution of charged, strongly hydrophilic, and less hydrophilic surface regions. We conclude that intuitive arguments based on DLVO forces may be put forward to predict the expected adsorption orientation of the proteins. However, observed differences in the relative adsorption amount of the two enzymes can only be explained by taking into account also protein–protein interactions and the stability of the aforementioned specific adsorption motifs.