Choosing a lipid force field for membrane remodeling: pore formation and membrane mimetics in CHARMM36, AMBER Lipid21 and Slipids

Lipid21 increases the pore formation barrier by 20–25 kJ/mol in DMPC, suppressing toroidal pore rearrangement and eliminating the metastable pore state under enhanced sampling.

• Why it matters: Force-field choice is often tuned for equilibrium properties, leaving uncertainty about how it affects membrane remodeling and pore formation during deformation.
• What they did: The study systematically compared AMBER Lipid21, CHARMM36, and Slipids-2020 using chain-coordinate collective variables for pore formation and HMMM for surface adhesion/remodeling.
• The result: Lipid21 exceeds the single experimental energy barrier estimate by a factor of 3 to 4, while all models reproduce the intended 10-fold diffusion increase in HMMM; only Lipid21 stays stable for 1 s without position restraints.