The adsorption of bovine serum albumin (BSA) onto a hydrophobic graphite surface is studied using molecular-dynamics simulation. In addition to the free, that is, unsteered, adsorption, we also investigate forced adsorption, in which the action of an AFM tip pushing the protein with constant force to the surface is modeled. Using an implicit inviscid water model, the adsorption dynamics and energetics are monitored for two different initial protein orientations toward the surface. In all cases, we find that the protein partially unfolds and spreads on the surface. The spreading is in agreement with the well-known high biocompatibility of graphite-based implants. The denaturation is, however, greatly enhanced in the case of forced adsorption. We follow the position of the so-called lipid-binding pocket found in subdomain IIIA (Sudlow site II) during adsorption and find that it is tilted and moved toward the graphite surface in all cases, in agreement with its hydrophobic character. The relevance of our findings for the common measurement procedure of studying protein adhesion using AFM experiments is discussed.

We present results from molecular dynamics simulations and contact angle measurements on graphite showing that this surface is indeed intrinsically mildly hydrophilic contrary to the common belief. Hydrocarbon contamination, known to be the source for the usually observed hydrophobic property of graphite, also affects protein adsorption processes as shown in this study. In the computational part of this work ethane was used as a model hydrocarbon which acts on the surface by reducing the water− surface and protein−surface interactions. This contamination then results in higher water contact angles. The process of protein adsorption is studied for the example of insulin revealing a reduction in adsorption strength despite the surface being more hydrophobic when contaminated. Although the proteins did not denature on the contaminated surfaces, further processes, such as the displacement of hydrocarbons by the protein, may occur on a longer time scale. In conclusion, we argue that proteins adsorb faster on pure than on contaminated surfaces with respect to the molecular dynamics time scale of ns.

The atomistic modeling of protein adsorption on surfaces is hampered by the different time scales of the simulation ( s) and experiment (up to hours), and the accordingly different ‘final’ adsorption conformations. We provide evidence that the method of accelerated molecular dynamics is an efficient tool to obtain equilibrated adsorption states. As a model system we study the adsorption of the protein BMP-2 on graphite in an explicit salt water environment. We demonstrate that due to the considerably improved sampling of conformational space, accelerated molecular dynamics allows to observe the complete unfolding and spreading of the protein on the hydrophobic graphite surface. This result is in agreement with the general finding of protein denaturation upon contact with hydrophobic surfaces.

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The adsorption of streptavidin is studied on two surfaces, graphite and titanium dioxide, using accelerated molecular dynamics. Adsorption on graphite leads to strong conformational changes while the protein spreads out over the surface. Interestingly, also adsorption on the highly hydrophilic rutile surface induces considerable spreading of the protein. We pin down the cause for this unfolding to the interaction of the protein with the ordered water layers above the rutile surface. For special orientations, the protein penetrates the ordered water layers and comes into direct contact with the surface where the positively charged amino acids settle in places adjacent to the negatively charged top surface atom layer of rutile. We conclude that for both surface materials studied, streptavidin changes its conformation so strongly that it loses its potential for binding biotin. Our results are in good qualitative agreement with available experimental studies.