Molecular dynamics simulation of lysozyme adsorption/desorption on hydrophobic surfaces

Abstract

In this work, we present a series of fully atomistic molecular dynamics (MD) simulations to study lysozyme's orientation-dependent adsorption on polyethylene (PE) surface in explicit water. The simulations show that depending on the orientation of the initial approach to the surface the protein may adsorb or bounce from the surface. The protein may completely leave the surface or reorient and approach the surface resulting in adsorption. The success of the trajectory to adsorb on the surface is the result of different competing interactions, including protein-surface interactions and the hydration of the protein and the hydrophobic PE surface. The difference in the hydration of various protein sites affects the protein's orientation-dependent behavior. Side-on orientation is most likely to result in adsorption as the protein-surface exhibits the strongest attraction. However, adsorption can also happen when lysozyme's longest axis is tilted on the surface if the protein-surface interaction is large enough to overcome the energy barrier that results from dehydrating both the protein and the surface. Our study demonstrates the significant role of dehydration process on hydrophobic surface during protein adsorption.

Figure 1

Snapshot of the simulation system at t=0 for one of the simulated trajectories. The box dimensions are 6.565 × 6.119 × 11.3 nm³ (X × Y × Z): lysozyme on PE surface (010) in water (gray) and counter ions, Cl⁻ (orange) capped with repulsive wall (green), projected in Y-Z plane. The polyethylene chains are aligned in the direction of the Y axis. The Z direction is normal to the PE surface.

Figure 2

Left: Definition of the protein-surface relative orientation, θ and protein-surface distance, z_ps Right: contour map of the frequency the protein visiting, I_oc, as a function of θ and z_ps, calculated from all 27 cases during the first 40 ns of simulation. Contour map of the frequency the protein visiting, I_oc, as a function of the orientation, θ, and distance from the surface, z_ps, calculated from all 27 cases during the first 40 ns of simulation. The grid spacing is 2° and 0.01 nm for θ and z_ps, respectively.

Figure 3

Contour map of the protein-surface interaction energy, E_ps, as a function of θ and z_ps calculated from all 27 trajectories during the first 40 ns of simulation. The color scale is in units of kT. White color represents lack of data.

Figure 4

Example of a process of lysozyme adsorption that involves two unsuccessful attempts before a third landing that results in adsorption. The entire process is monitored by looking at the protein-surface distance z_ps (A), the adsorption angle θ (B), and the protein-surface interaction energy E_ps (C).

Figure 5

Distance between the surface and center of mass of the protein’s residues, z_α. The red line corresponds to the first landing (t=1.994 ns) and the black line corresponds to the third (t=7.529 ns), respectively.

Figure 6

(A) Bulk interaction energy between the water and the residues involved in the first (14 and 126–129, in red) and third (67–71, 81, in black) landing, respectively. (B) The proximal radial distribution function, pG(r), corresponding to the same two landing sites.

Figure 7

The top panel shows the protein-surface interaction energy, E_ps ,as a function of time. The two red arrows indicate the times of relevant events during this unsuccessful adsorption attempt, 1.994 and 2.058 ns. The two bottom panels show snapshots of the system at the indicated times. The residues characterized as the landing site (14 and 126–129) are shown in orange.