Accelerating Membrane Simulations with Hydrogen Mass Repartitioning

J Chem Theory Comput. 2019 Aug 13;15(8):4673-4686. doi: 10.1021/acs.jctc.9b00160. Epub 2019 Jul 2.


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.

MeSH terms

  • Cell Membrane / chemistry*
  • Diffusion
  • Glycophorins / chemistry
  • Humans
  • Hydrogen / chemistry*
  • Lipid Bilayers / chemistry*
  • Membrane Proteins / chemistry*
  • Molecular Dynamics Simulation*
  • Motion
  • Peptides / chemistry
  • Phosphatidylcholines / chemistry
  • Protein Multimerization
  • Receptors, G-Protein-Coupled / chemistry
  • Thermodynamics


  • Glycophorins
  • Lipid Bilayers
  • Membrane Proteins
  • Peptides
  • Phosphatidylcholines
  • Receptors, G-Protein-Coupled
  • Hydrogen
  • 1-palmitoyl-2-oleoylphosphatidylcholine