Accelerating Membrane Simulations with Hydrogen Mass Repartitioning

Abstract

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.

Outer membrane protein size and LPS O-antigen define protective antibody targeting to the Salmonella surface

“…A 2-fs time step was used for the first 250 ns, after which hydrogen mass repartitioning (HMR) was employed to reach a time step of 4 fs for the remainder of the simulations. HMR has recently been demonsrated to be applicable to membrane-protein systems with little to no effect on dynamics 55 . For the steered MD simulation, a murine IgG1 antibody (taken from PDB 1IGY) was added to the STm-B system and pulled towards the OmpD loops at 1.0 Å/ns for 70 ns.…”

Advances in Molecular Dynamics Simulations and Enhanced Sampling Methods for the Study of Protein Systems

“…Hopkins et al tested HMR on various benchmark systems, ranging from 3-residue peptide to 129-residue protein, hen egg white lysozyme (HEWL), and concluded there is no significant difference in kinetics and thermodynamics when HMR is used [ 30 ]. Balusek et al assessed the validity of HMR for the membrane simulation, and figured out most structural properties (area-per-lipid, electron density profile, order parameters) being identical, but some kinetic properties such as diffusion constant showed some differences [ 31 ].…”

Molecular-dynamics-simulation-guided membrane engineering of Saccharomyces cerevisiae by overexpression of plant FAE1 and GPAT5 genes increases fatty acid chain length in membrane lipids

“…An in-house Python script was used to implement the hydrogen mass repartitioning approach (41) to remove the fastest degrees of freedom in the system, allowing the use of time steps up to 4 fs in the MD simulations. The hydrogen mass was increased by a factor of four, from 1.008 u to 4.0320 u.…”

“…The hydrogen mass was increased by a factor of four, from 1.008 u to 4.0320 u. This approach has been tested in simulations of a variety of membranes, showing practically no differences in their structural properties when compared to non-heavy hydrogen simulations (41). At least three independent replicates were collected for each system (Table 1), using different initial random seeds for the simulation (42,43).…”