Free energy of adsorption of proteins at fluid/solid interfaces using molecular simulation

Protein adsorption on solid surfaces is widespread in chemical engineering and beyond. It is desirable to be able to predict the free energy of adsorption of proteins for the design of surfaces and solvents that either enhance or reduce protein adsorption (e.g. for chromatography and detergents respectively). Whilst methods for estimation of the free energy do exist, they are largely empirical or based on severe assumptions. An example of the latter is the assumption that proteins undergo no major conformational change upon adsorption - our prior work (and that of others) clearly shows this is unlikely to be satisfied in general. We have, therefore, developed two methods for estimating the free energy of protein adsorption that avoids this assumption - a computationally expensive but in principle accurate technique based on molecular dynamics (MD) simulation, and a second much quicker technique based on global molecular mechanics that is able to yield estimates that are comparable to those predicted by MD. These two methods are presented and demonstrated by considering the adsorption of met-enkephalin at the gasgraphite interface.