For both equilibration and production simulations, isotropic pressure coupling was used, with the Berendsen 187 barostat used during equilibration, and the Parrinello- For both AA and CG pore simulations, we used the GROMACS 7 simulation package to run the lipid pore umbrella sampling simulations (version 2018 for AA and Martini 2 systems, version 2021 for the Martini 3 versions). We followed the reaction coordinate described by Hub and Awasthi 8 implemented using PLUMED 9 version 2.5.0. 40 or 48 umbrella windows were used per AA or CG system, respectively, with force constants between 5000 and 17000 kJ mol -1 . Simulation times were 66 ns for the AA systems and between 730 and 2100 ns for the CG systems (reaction coordinates were sampled every 10 ps for AA systems and every 20 ps for CG ones). The same pore reaction coordinate settings were employed for AA and CG systems: the coordinate was computed over 20 cylindrical slices, of 0.2 nm thickness and 1.2 nm radius, with a slice occupancy switch function ζ parameter of 0.25. Because of the different resolutions, the reaction coordinate values are not directly comparable between AA and CG; still, the energy differences between PMF minima (the unbiased membrane state) and the inflection points (onset of defect formation) can be compared. The CHARMM36 force field was used for all AA proe simulations. Membranes were built using CHARMM-GUI and equilibrated according to its protocol. Systems had 144 DPPC lipids per leaflet, solvated with ~13300 TIP3P water molecules with 150 mM NaCl ionic strength, in a 9.5×9.5×7.5 cubic box. Particle-Mesh Ewald 13 (PME) summation was used to compute electrostatics and Van der Waals interactions were switched off smoothly from 1.0 to 1.2 nm. The Verlet list scheme was employed to update the particle neighbor list. A Nosé-Hoover 14 thermostat with a coupling time of 1.0 ps was used to maintain the temperature at 323 K. A semi-isotropic pressure coupling to 1.0 bar was employed using the Parrinello-Rahman 15 barostat with a relaxation time of 5.0 ps. The PMF was estimated using the WHAM program by Alan Grossfield version 2.0.11.