Taking the Monte‐Carlo gamble: How not to buckle under the pressure

Consistent buckling distortions of a large membrane patch (200 × 200 Å) are observed during molecular dynamics (MD) simulations using the Monte‐Carlo (MC) barostat in combination with a hard Lennard–Jones (LJ) cutoff. The buckling behavior is independent of both the simulation engine and the force field but requires the MC barostat‐hard LJ cutoff combination. Similar simulations of a smaller patch (90 × 90 Å) do not show buckling, but do show a small, systematic reduction in the surface area accompanied by ~1 Å thickening suggestive of compression. We show that a mismatch in the way potentials and forces are handled in the dynamical equations versus the MC barostat results in a compressive load on the membrane. Moreover, a straightforward application of elasticity theory reveals that a minimal compression of the linear dimensions of the membrane, inversely proportional to the edge length, is required for buckling, explaining this differential behavior. We recommend always using LJ force or potential‐switching when the MC barostat is employed to avoid undesirable membrane deformations. Significant distortions of a large bio‐membrane (lipid bilayer) are noted when a specific combination of molecular dynamics simulation parameters is employed (Monte‐Carlo (MC) barostat and Lennard–Jones hard cutoff (≤10 Å)). Other factors, such as molecular dynamics engine and protein force field are not causative. Smaller membrane patches simulated with the problematic combination show compressive effects but do not buckle. Nonetheless, we strongly suggest caution when using this parameter combination to simulate membrane systems.