Calculation of conformational free energies by confinement simulations in explicit water with implicit desolvation

摘要

The confinement method is a robust and conceptually simple free energy simulation method that allows the calculation of conformational free energy differences between highly dissimilar states. Application of the method to explicitly solvated systems requires a multi-stage simulation protocol for the calculation of desolvation free energies. Here we show that these desolvation free energies can be readily obtained from an implicit treatment, which is simpler and less costly. The accuracy and robustness of this protocol was shown by the calculation of conformational free energy differences of a series of explicitly solvated test systems. Given the accuracy and ease by which these free energy differences were obtained, the confinement method is promising for the treatment of conformational changes in large and complex systems.