Computer Simulation of Protein Adsorption to a Material Surface in Aqueous Solution: Biomaterials Modeling of a Ternary System

Biomaterals are often in contact with the body or body fluids, so interfacial phenomena, especially protein adsorption, control essential parameters, such as biocompatability and bioreactivity. In addition, optimization of biotechnology tools such as DNA/protein microarrays and microfluidic systems will also require a mechanistic understanding of how biological macromolecules interact with materials surfaces. Thus, atomistic characterization of structure−function relationships at the interface between biological macromolecules and materials surfaces will be crucial to the future development of an enormous range of bioengineering and biotechnology applications. We have used standardized computer modeling software to simulate protein adsorption to a materials surface in water. Molecular dynamics and local minimization were employed to simulate a multicomponent system in which a hydrated protein, bovine pancreatic trypsin inhibitor (BPTI), encounters an MgO surface in pure water. It is known that soluble proteins bind to charged materials surfaces in water and in vivo. Our simulations show adsorption of BPTI to MgO in water with binding energies of 242, 350, and 241 kcal/mol for three different initial protein orientations. Importantly, our results show that in this aqueous system there is very little interaction between the atoms of the protein and those of the surface. Crucial binding events at the surface are mediated by the solvation layer in the interphase (double-layer) region. This result is expected on the basis of classical electrochemical theory but is usually not explicitly considered in the protein adsorption literature. The present work provides a model for the manner in which the interfacial water facilitates protein adsorption and suggests that the scope of the water's influence may be relatively long-range.