A novel approach to calculate protein adsorption isotherms by molecular dynamics simulations

Protein adsorption plays a role in many fields, where in some it is desirable to maximize the amount adsorbed, in others it is important to avoid protein adsorption altogether. Therefore, theoretical methods are needed for a better understanding of the underlying processes and for the prediction of adsorption quantities. In this study, we present a proof-of-concept that the calculation of protein adsorption isotherms by molecular dynamics (MD) simulations is possible using the steric mass action (SMA) theory. Here we are investigating the adsorption of bovine/human serum albumin (BSA/HSA) and hemoglobin (bHb) on Q Sepharose FF. Protein adsorption isotherms were experimentally determined and modeled. Free energy profiles of protein adsorption were calculated by MD simulations to determine the Henry isotherms as a first step. Although each simulation contained only one protein, notably the calculated isotherms are in reasonably good agreement with the experimental isotherms. Hence, we could show that MD data can lead to protein adsorption data in good agreement with experimental data. The results were critically discussed and requirements for future applications are identified.