Process and thermodynamics of ligand–receptor interaction studied using a novel simulation method

A novel simulation method for unbinding a ligand from its receptor is described. It requires no prior knowledge of the unbinding trajectory and has atomic resolution. It places forces of equal magnitude but opposite directions on the two molecules, and lets the system locate an unbinding trajectory. The mutual repulsion method has been applied successfully to the bovine serum retinol-binding protein / retinol complex. A change in water structure has been observed during the unbinding process. The free energy change of unbinding has also been evaluated, and the value compares favourably with the experimental result.