Accelerating Membrane Simulations with Hydrogen Mass Repartitioning

The time step of
atomistic molecular dynamics (MD) simulations is determined by the
fastest motions in the system and is typically limited to 2 fs. An
increasingly popular approach is to increase the mass of the hydrogen
atoms to ∼3 amu and decrease the mass of the parent atom by
an equivalent amount. This approach, known as hydrogen-mass repartitioning
(HMR), permits time steps up to 4 fs with reasonable simulation stability.
While HMR has been applied in many published studies to date, it has
not been extensively tested for membrane-containing systems. Here,
we compare the results of simulations of a variety of membranes and
membrane–protein systems run using a 2 fs time step and a 4
fs time step with HMR. For pure membrane systems, we find almost no
difference in structural properties, such as area-per-lipid, electron
density profiles, and order parameters, although there are differences
in kinetic properties such as the diffusion constant. Conductance
through a porin in an applied field, partitioning of a small peptide,
hydrogen-bond dynamics, and membrane mixing show very little dependence
on HMR and the time step. We also tested a 9 Å cutoff as compared
to the standard CHARMM cutoff of 12 Å, finding significant deviations
in many properties tested. We conclude that HMR is a valid approach
for membrane systems, but a 9 Å cutoff is not.