All simulations used the C36 FF
for lipids16 (link),17 (link) and the CHARMM TIP3P water model.43 (link)−45 (link) To get better sampling and check the convergence, five independent
MD simulations were performed for each bilayer system using NAMD,
GROMACS, AMBER, and OpenMM. The simulation temperature was maintained
above the transition temperature of each bilayer: 300.0 (POPS), 303.15
(DOPC/POPC), 310.0 (POPE), and 323.15 K (DPPC/PSM). In addition, the
pressure was maintained at 1 bar. PBC were employed for all simulations,
and the particle mesh Ewald (PME) method30 (link) was used for long-range electrostatic interactions. The simulation
time step was set to 2 fs in conjunction with the SHAKE algorithm46 (link) to constrain the covalent bonds involving hydrogen
atoms for all programs except GROMACS in which the LINCS algorithm47 (link) was used. After the standard Membrane
Builder minimization and equilibration steps, the production
run of each simulation was performed for 250 ns. The optimal parameters
were determined using the most recent version of each program (NAMD
2.9, GROMACS 5.0, AMBER14, and OpenMM 6.2), such that the use of previous
versions can cause some problems. For example, the semi-isotropic
pressure coupling method was not implemented until version 6.2 of
OpenMM. The individual simulation protocols that we tested for each
MD program are summarized inTable 1 and described in detail below.
for lipids16 (link),17 (link) and the CHARMM TIP3P water model.43 (link)−45 (link) To get better sampling and check the convergence, five independent
MD simulations were performed for each bilayer system using NAMD,
GROMACS, AMBER, and OpenMM. The simulation temperature was maintained
above the transition temperature of each bilayer: 300.0 (POPS), 303.15
(DOPC/POPC), 310.0 (POPE), and 323.15 K (DPPC/PSM). In addition, the
pressure was maintained at 1 bar. PBC were employed for all simulations,
and the particle mesh Ewald (PME) method30 (link) was used for long-range electrostatic interactions. The simulation
time step was set to 2 fs in conjunction with the SHAKE algorithm46 (link) to constrain the covalent bonds involving hydrogen
atoms for all programs except GROMACS in which the LINCS algorithm47 (link) was used. After the standard Membrane
Builder minimization and equilibration steps, the production
run of each simulation was performed for 250 ns. The optimal parameters
were determined using the most recent version of each program (NAMD
2.9, GROMACS 5.0, AMBER14, and OpenMM 6.2), such that the use of previous
versions can cause some problems. For example, the semi-isotropic
pressure coupling method was not implemented until version 6.2 of
OpenMM. The individual simulation protocols that we tested for each
MD program are summarized in
