Due to the presence of the gradient-dependent drift forces, the pressure is not a well-defined quantity of the system. In our previous work, we showed that the drift forces uphold a pressure gradient in the box according to P(s) = s -3 P * , which suggests that the average pressure of the system is not meaningful. To be able to calculate accurate free-energy differences at constant pressure, an extension of the method to NPT conditions is crucial. A possible avenue would be to rely on a coupling involving solely the pressure of the FG region, which can be calculated using the volume-averaging method. The implementation of this approach will also require an adaptation of the biasing procedure to NPT simulations.