PME Switching in Confinement Simulations of Charged Solutes.

Abstract

The confinement method is a reaction coordinate-free enhanced sampling method for the calculation of conformational free energy differences. We show that in explicit solvent, artifacts occur when treating charged solutes. These artifacts are resolved by switching off the particle mesh Ewald (PME) method at the start of confinement. Calculations of the free energy cost of this switching converge rapidly, with small statistical error. The effectiveness and accuracy of confinement with PME switching is demonstrated by its application to a series of solutes of different charge; its ability to treat complex systems is illustrated by evaluating the free energy difference between B and Z-DNA.