Six equilibration runs were performed (Table ), where the restraints were progressively removed. The first two are NVT runs, where the velocity rescaling thermostat is employed, 37 with 1 ps time constant and temperature set to 303.15 K, which is above the phase transition temperature of the POPC bilayer. Three different groups are coupled separately due to the different rates of diffusion of the three phases: i) the protein ii) the bilipid membrane iii) water and ions. The four remaining equilibration runs are NPT, where semi-isotropic pressure coupling (isotropic in the x and y direction, but different in the z direction, to allow the bilayer to deform in the xy plane independently of the z-axis) is applied through the Berendsen barostat with a coupling constant of 5 ps and a reference pressure of 1 bar and 4.5 • 10 -5 bar -1 compressibility.