Molecular Dynamics Simulations of Hen Egg White Lysozyme Adsorption at a Charged Solid Surface

Abstract

Hen egg white lysozyme (HEWL) adsorption on negatively charged, hydrophilic surfaces has been investigated using atomistic molecular dynamics. Analysis of six 20 ns trajectories performed at pH 7 and ionic strength 0.02 M (NaCl) reveals that conformational alterations are required for HEWL adsorption, and that upon adsorption the protein loses some alpha-helical content. Simulations for a few different initial orientations show that the HEWL protein adsorbs on a flat surface with an angle between the protein long axis and the surface of about 45 degrees . The main adsorption site is located on the N,C-terminal part of the HEWL surface; the major role is played by Lys1, Arg5, Arg14, and Arg128. Adsorption is not found with contrary orientations. Two additional 20 ns trajectories calculated with 0.5 M ionic strength suggest that the main force governing adsorption is electrostatic attraction between parts of the protein and the surface. A trajectory obtained for the protein situated inside a cubic box built from the charged surfaces shows that the adsorption pattern is different for flat and nonflat surfaces, and in particular, adsorption on the nonflat surface requires tertiary structure alterations and partial unfolding. The observed trends are consistent with both experimental and previous computational studies.

Formation of Silica-Lysozyme Composites Through Co-Precipitation and Adsorption

“…These authors attributed the "missing" space between particles as an indication for the near-complete loss of structural coherence of the lysozyme molecule upon adsorption to multiple silica spheres. This was supported by other studies showing that lysozyme can lose substantial amounts of its secondary (transformation of α-helixes to β-sheets) and tertiary structure (more oblate molecules), especially when adsorbed to non-flat surfaces (Kubiak and Mulheran, 2009), porous media (Hao et al, 2014), or in between nanoparticles (Gagner et al, 2011). This is in agreement with the energy-filtered images shown in Figure 4, which indicate that lysozyme molecules underwent substantial conformational changes upon adsorption onto silica particles and incorporation into composites in both syntheses.…”

“…The structural changes become more significant when lysozyme is adsorbed onto non-flat surfaces such as nanoparticle surfaces with strong curvature (Kubiak and Mulheran, 2009;Gagner et al, 2011;Hao et al, 2014). Due to the partial unfolding, the more hydrophobic core of the lysozyme molecule is exposed.…”

Understanding protein adsorption phenomena at solid surfaces

“…Compromises are typically made by treating solvent molecules implicitly via an effective dielectric medium or by using force fields that have no extra term for H-bonds [275][276][277][278][279]. In quite a number of recent studies empirical all-atoms force field methods were successfully applied to determine the preferred orientations of surface bound proteins [275][276][277][278][280][281][282][283][284][285][286], to visualize conformational rearrangements upon adsorption [276][277][278]287], and to explore effects on the solvation shell [277,288,289]. By using a combination of MC and MD simulations to study the adsorption of the proteins IgG and cytochrome c (Cyt-c), Zhou et al were able to show that there is a surface charge-driven mechanism of protein orientation [281][282][283].…”

Fibronectin Module FNIII9 Adsorption at Contrasting Solid Model Surfaces Studied by Atomistic Molecular Dynamics

“…Therefore only local structural changes are induced by the adsorption, which agrees well with previous MD adsorption studies. [15][16][17][18]21,22,26 Of the anchoring residues, lysine and arginine are positively charged, and serine is polar.…”