Sunday, March 01, 2015

Steps to Perform a Simulation

Below is presented a generalised procedure for performing a simulation. The exact steps and processes involved will vary depending on exactly what is being attempted. Use as a general guide only!

  1. Clearly identify the property / phenomena of interest to be studied by performing the simulation. Do not continue further until you are clear on this!
  2. Select the appropriate tools to be able to perform the simulation and observe the property / phenomena of interest. It is important to read and familiarise yourself with publications by other researchers on similar systems. Tools include:

    - software to perform the simulation with, consideration of force field may influence this decision.

    force field which describes how the atoms / particles within the system interact with each other. Select one that is appropriate for the system being studied and the property / phenomena of interest. Very important and non-trivial step! Consider now how you will analyze your simulation data to make your observations.
  3. Obtain / generate the initial coordinate file for each molecule to be placed within the system. The page linked there has some software suggestions.
  4. Generate the raw starting structure for the system by placing the molecules within the coordinate file as appropriate. Molecules may be specifically placed or arranged randomly.
  5. Obtain / generate the topology file for the system, using (for example)
    SwissParam (for CHARMM forcefield), 
    PRODRG (for ffgmx/GROMOS96 43A1), 
    Automated Topology Builder (for GROMOS96 53A6), 
    MKTOP (for OPLS/AA) or
    - your favourite text editor in concert with chapter 5 of the
    GROMACS Manual.
    - For the 
    AMBER force fields, antechamber or acpype might be appropriate.
  6. Describe a simulation box (e.g. using editconf) whose size is appropriate for the eventual density you would like, fill it with solvent (e.g. using genbox), and add any counter-ions needed to neutralize the system (e.g. using grompp and genion). In these steps you may need to edit your topology file to stay current with your coordinate file.
  7. Run an energy minimization on the system (using grompp and mdrun). This is required to sort out any bad starting structures caused during generation of the system, which may cause the production simulation to crash. It may be necessary also to minimize your solute structure in vacuo before introducing solvent molecules (or your lipid bilayer or whatever else). You should consider using flexible water models and not using bond constraints or frozen groups. The use of position restraints and/or distance restraints should be evaluated carefully.
  8. Select the appropriate simulation parameters for the equilibration simulation (defined in .mdp file). You need to choose simulation parameters that are consistent with how force field was derived. You may need to simulate at NVT with position restraints on your solvent and/or solute to get the temperature almost right, then relax to NPT to fix the density (which should be done with Berendsen until after the density is stabilized, before a further switch to a barostat that produces the correct ensemble), then move further (if needed) to reach your production simulation ensemble (e.g. NVTNVE). If you have problems here with the system blowing up, consider using the suggestions on that page, e.g. position restraints on solutes, or not using bond constraints, or using smaller integration timesteps, or several gentler heating stage(s).
  9. Run the equilibration simulation for sufficient time so that the system relaxes sufficiently in the target ensemble to allow the production run to be commenced (using grompp and mdrun, then g_energy and trajectory visualization tools).
  10. Select the appropriate simulation parameters for the production simulation (defined in .mdp file). In particular, be careful not to re-generate the velocities. You still need to be consistent with how the force field was derived and how to measure the property / phenomena of interest.
  11. Run the production simulation for sufficient time so that property / phenomena of interest can be observed in required detail (using grompp / tpbconv and mdrun).
  12. Analyse / visualise the resulting trajectory and data files to obtain information on the property / phenomena of interest.


  • see REMD for additional information on steps for a replica-exchange simulation


  • Flow Chart - simple flow chart of a typical GROMACS MD run of a protein in a box of water.
  • GROMACS Flowsheet - flowsheet of the general procedure for performing a molecular dynamic simulation using GROMACS. Shows linkage between files required and generated in each step and general command lines used.
Post a Comment