Molecular-Level Understanding of Protein Adsorption at the Interface between Water and a Strongly Interacting Uncharged Solid Surface

Abstract

Although protein adsorption on solids is of immense relevance, experimental limitations mean there is still a remarkable lack of understanding of the adsorption mechanism, particularly at a molecular level. By subjecting 240+ molecular dynamics simulations of two peptide/water/solid surface systems to statistical analysis, a generalized molecular level mechanism for peptide adsorption has been identified for uncharged surfaces that interact strongly with the solution phase. This mechanism is composed of three phases: (1) biased diffusion of the peptide from the bulk phase toward the surface; (2) anchoring of the peptide to the water/solid interface via interaction of a hydrophilic group with the water adjacent to the surface or a strongly interacting hydrophobic group with the surface; and (3) lockdown of the peptide on the surface via a slow, stepwise and largely sequential adsorption of its residues, which we term 'statistical zippering'. The adsorption mechanism is dictated by the existence of water layers adjacent to the solid and orientational ordering therein. By extending the solid into the solution by ~8 Å and endowing it with a charged character, the water layers ensure the peptide feels the effect of the solid at a range well beyond the dispersion force that arises from it, thus inducing biased diffusion from afar. The charging of the interface also facilitates anchoring of the peptide near the surface via one of its hydrophilic groups, allowing it time it would otherwise not have to rearrange and lockdown. Finally, the slowness of the lockdown process is dictated by the need for the peptide groups to replace adjacent tightly bound interfacial water.

What makes a good graphene-binding peptide? Adsorption of amino acids and peptides at aqueous graphene interfaces

“…This local minimum is related to the 'solvent mediated' adsorption of the AAs, where the AA is separated from the graphene interface by the first layer of interfacial water molecules. This 'solvent mediated' minimum has also been observed for the adsorption of AAs and peptides at metal interfaces, 18,78,79 particularly for silver, 18,80 and mineral 26,30 interfaces.…”

Modeling and simulation of protein–surface interactions: achievements and challenges

“…Drawing conclusions from a statistically inadequate sampling will thus often lead to incorrect interpretations. To improve the statistical significance of their sampling, Penna et al (2014) chose a direct approach and performed more than 240 explicit solvent MD simulations for the investigation of adsorption mechanisms of a platinum-binding peptide and a gold-binding peptide on neutral Pt(111) and Au (111) surfaces, respectively. From these simulations, they obtained statistics on many binding characteristics, such as anchoring events between each of the peptide residues and the surfaces and the distribution of transition times from the anchoring phase to the initial lockdown phase.…”

Molecular mechanics models for the image charge, a comment on “including image charge effects in the molecular dynamics simulations of molecules on metal surfaces”

“…Furthermore, this bias would be problematic when simulating other polar groups such as in biomolecules and ionic liquids. 8,9 To fix this "asymmetry" issue, we have devised a symmetric model, where the nucleus has no charge, but has two particles attached to it, which form a line and are of opposite charge (R − -Pt-R + ). To keep a sound description with an identical dipole moment, we have increased the length and decreased the charge of the particles accordingly, as described in the supporting information.…”