Calculation of adsorption free energy for solute-surface interactions using biased replica-exchange molecular...

The adsorption behavior of a biomolecule, such as a peptide or protein, to a functionalized surface is of fundamental importance for a broad range of applications in biotechnology. The adsorption free energy for these types of interactions can be determined from a molecular dynamics simulation using the partitioning between adsorbed and nonadsorbed states, provided that sufficient sampling of both states is obtained. However, if interactions between the solute and the surface are strong, the solute will tend to be trapped near the surface during the simulation, thus preventing the adsorption free energy from being calculated by this method. This situation occurs even when using an advanced sampling algorithm such as replica-exchange molecular dynamics (REMD). In this paper, the authors demonstrate the fundamental basis of this problem using a model system consisting of one sodium ion (Na(+)) as the solute positioned over a surface functionalized with one negatively charged group (COO(-)) in explicit water. With this simple system, the authors show that sufficient sampling in the coordinate normal to the surface cannot be obtained by conventional REMD alone. The authors then present a method to overcome this problem through the use of an adaptive windowed-umbrella sampling technique to develop a biased-energy function that is combined with REMD. This approach provides an effective method for the calculation of adsorption free energy for solute-surface interactions.