We use the simulation protocol described in detail by Gapsys et al . A 2 fs timestep was used throughout. For all simulations following minimisation, the stochastic dynamics integrator was used keeping the temperature at 298 K with an inverse friction of 2 ps. Pressure was held at 1 bar using the Parinello-Rahman barostat with a time constant of 5 ps. Long range coulomb interactions were treated using Particle Mesh Ewald (PME) with a real space cutoff of 1.1 nm, using a relative strength at the cutoff of 1e-5. Fourier grid spacing was set to 0.12 nm, and van der Waals interactions were smoothly switched off between 1.0 and 1.1 nm, with dispersion correction for both energy and pressure applied. For bonds to hydrogen atoms, bond lengths were constrained using the LINCS algorithm . For alchemical transitions the van der Waals and electrostatic interactions were soft-cored .