Useful mdrun features

This section discusses features in gmx mdrun that don’t fit well elsewhere.

Re-running a simulation

The rerun feature allows you to take any trajectory file traj.trr and compute quantities based upon the coordinates in that file using the model physics supplied in the topol.tpr file. It can be used with command lines like mdrun -s topol -rerun traj.trr. That tpr could be different from the one that generated the trajectory. This can be used to compute the energy or forces for exactly the coordinates supplied as input, or to extract quantities based on subsets of the molecular system (see gmx convert-tpr and gmx trjconv). It is easier to do a correct “single-point” energy evaluation with this feature than a 0-step simulation.

Neighbor searching is normally performed for every frame in the trajectory, since gmx mdrun can no longer assume anything about how the structures were generated. If nstlist is zero, then only one neighbor list will be constructed. Naturally, no update or constraint algorithms are ever used.

Running a simulation in reproducible mode

It is generally difficult to run an efficient parallel MD simulation that is based primarily on floating-point arithmetic and is fully reproducible. By default, gmx mdrun will observe how things are going and vary how the simulation is conducted in order to optimize throughput. However, there is a “reproducible mode” available with mdrun -reprod that will systematically eliminate all sources of variation within that run; repeated invocations on the same input and hardware will be binary identical. However, running in this mode on different hardware, or with a different compiler, etc. will not be reproducible. This should normally only be used when investigating possible problems.

Running multi-simulations

There are numerous situations where running a related set of simulations within the same invocation of mdrun are necessary or useful. Running a replica-exchange simulation requires it, as do simulations using ensemble-based distance or orientation restraints. Running a related series of lambda points for a free-energy computation is also convenient to do this way.

This feature requires configuring |Gromacs| with an external MPI library so that the set of simulations can communicate. The n simulations within the set can use internal MPI parallelism also, so that mpirun -np x mdrun_mpi for x a multiple of n will use x/n ranks per simulation.

There are two ways of organizing files when running such simulations. All of the normal mechanisms work in either case, including -deffnm.

-multidir

You must create a set of n directories for the n simulations, place all the relevant input files in those directories (e.g. named topol.tpr), and run with mpirun -np x gmx_mpi mdrun -s topol -multidir <names-of-directories>. If the order of the simulations within the multi-simulation is significant, then you are responsible for ordering their names when you provide them to -multidir. Be careful with shells that do filename globbing dictionary-style, e.g. dir1 dir10 dir11 ... dir2 .... This option is generally the most convenient to use. gmx mdrun -table for the group cutoff-scheme works only in this mode.

-multi

You must organize that the filenames for each simulation in a set of n simulations have an integer 0 through n-1 appended to the filename (e.g. topol2.tpr), and run with mpirun -np x gmx mdrun -multi n -s input. The order of simulations within the set is determined by the integer appended.

Examples running multi-simulations

mpirun -np 32 gmx_mpi mdrun -multi

Starts a multi-simulation on 32 ranks with as many simulations n as there are files named topol*.tpr for integers 0 to n-1. Other input and output files are suffixed similarly.

mpirun -np 32 gmx_mpi mdrun -multidir a b c d

Starts a multi-simulation on 32 ranks with 4 simulations. The input and output files are found in directories a, b, c, and d.

mpirun -np 32 gmx_mpi mdrun -multidir a b c d -gputasks 0000000011111111

Starts the same multi-simulation as before. On a machine with two physical nodes and two GPUs per node, there will be 16 MPI ranks per node, and 8 MPI ranks per simulation. The 16 MPI ranks doing PP work on a node are mapped to the GPUs with IDs 0 and 1, even though they come from more than one simulation. They are mapped in the order indicated, so that the PP ranks from each simulation use a single GPU. However, the order 0101010101010101 could run faster.

Running replica-exchange simulations

When running a multi-simulation, using gmx mdrun -replex n means that a replica exchange is attempted every given number of steps. The number of replicas is set with the -multi or -multidir option, described above. All run input files should use a different value for the coupling parameter (e.g. temperature), which ascends over the set of input files. The random seed for replica exchange is set with -reseed. After every exchange, the velocities are scaled and neighbor searching is performed. See the Reference Manual for more details on how replica exchange functions in GROMACS.

Controlling the length of the simulation

Normally, the length of an MD simulation is best managed through the [.mdp] option [nsteps](#nsteps), however there are situations where more control is useful. gmx mdrun -nsteps 100 overrides the [.mdp] file and executes 100 steps. gmx mdrun -maxh 2.5 will terminate the simulation shortly before 2.5 hours elapse, which can be useful when running under cluster queues (as long as the queuing system does not ever suspend the simulation).

Running a membrane protein embedding simulation

This is a module to help embed a membrane protein into an equilibrated lipid bilayer at a position and orientation specified by the user.

This method was initially described as a ProtSqueeze technique (Yesylevskyy S.O., J Chem Inf Model 47(5) (2007) 1986-94) and later implemented in GROMACS as g_membed tool (Wolf et al, J Comp Chem 31 (2010) 2169-2174). Currently the functionality of g_membed is available in mdrun if -membed option is specified (see below).

The main advantage is that it is possible to use very complex lipid bilayers with a number of different components that have been relaxed for a long time in a previous simulation. In theory that could be accomplished with a procedure similar to gmx solvate, but since lipids are much larger than water molecules it will lead to a large vacuum layer between the protein and membrane if we remove all molecules where any atom is overlapping. Instead, this module works by first artificially shrinking the protein in the xy-plane, then it removes lipids that overlap with a much smaller core, after which we gradually push the protein atoms back to their initial positions, while using normal dynamics for the rest of the system so lipids adapt to the protein.

To use membrane embedding, start by building a lipid bilayer that is just-so-slightly larger in the xy-plane than what you expect to need in the end, and make sure you have enough water outside the membrane to accommodate globular domains. Place the protein in the same coordinate file (and topology) as your lipid bilayer, and make sure it is in the orientation and position you want right in the middle of the bilayer.

The first settings have to be entered in the mdp file that controls your simulation. You need an energy group corresponding to your protein, this group should be frozen (all dimensions), and we should exclude all interactions inside the protein to avoid problems when it is distorted. For instance:

integrator     = md
energygrps     = Protein
freezegrps     = Protein
freezedim      = Y Y Y
energygrp_excl = Protein Protein

You will also need a number of settings for the actual membrane embedding process. These are entered as similar name and value pairs, but in the separate text data file embed.dat that you provide as the argument to the -membed option (we refer to the below when explaining the process). The embedding works in for stages:

1. The protein is resized around its center of mass by a factor xy in the xy-plane (the bilayer plane), and a factor z along the z-axis (normal to the bilayer). If the height of the protein is the same or smaller than the thickness of the membrane, a z-fraction larger than 1.0 can prevent the protein from being enveloped by the lipids.
2. All lipid and solvent molecules overlapping with the resized protein are removed. All interactions inside the protein are turned off to prevent numerical issues for small values of the scaling fractions.
3. A single md step is performed, where atoms in the rest of the system are moved.
4. The resize factors are adjusted by the small amounts (1-xy)/nxy and (1-z)/nz, where nxy and nz are the number of iterations to use. The resize factor for the xy-plane is adjusted first. The resize factor for the z-direction is not changed until the xy factor is 1.0 (after nxy iterations).
5. Steps 3 and 4 are repeated until the protein has again reached its original size, i.e. after nxy+nz iterations. After the embedding you might still want to perform a short relaxation.

Parameters that can be specified in embed.dat, with default values that will be used if the setting is omitted:

• xyinit (0.5) Resize factor for the protein in the xy dimension before starting embedding.
• xyend (1.0) Final resize factor in the xy dimension.

• zinit (1.0) Resize factor for the protein in the z

  dimension before starting embedding.

• zend (1.0) Final resize faction in the z dimension.
• nxy (1000) Number of iteration for the xy dimension.
• nz (0) Number of iterations for the z dimension.
• rad (0.22) Probe radius to check for overlap between the group to embed and the membrane.
• pieces (1) Perform piecewise resize. Select parts of the group to insert and resize these with respect to their own geometrical center.
• asymmetry (no) Allow asymmetric insertion, i.e. the number of lipids removed from the upper and lower leaflet will not be checked.
• ndiff (0) Number of lipids that will additionally be removed from the lower (negative number) or upper (positive number) membrane leaflet.
• maxwarn (0) Largest number of membed warnings allowed.