.. _gmx-sysprep:
System preparation
==================
.. toctree::
:hidden:
There are many ways to prepare a simulation system to run with
|Gromacs|. These often vary with the kind of scientific question being
considered, or the model physics involved. A protein-ligand atomistic
free-energy simulation might need a multi-state topology, while a
coarse-grained simulation might need to manage defaults that suit
systems with higher density.
Steps to consider
-----------------
The following general guidance should help with planning successful
simulations. Some stages are optional for some kinds of simulations.
1. Clearly identify the property or phenomena of interest to be
studied by performing the simulation. Do not continue further until
you are clear on this! Do not run your simulation and then seek to
work out how to use it to test your hypothesis, because it may be
unsuitable, or the required information was not saved.
2. Select the appropriate tools to be able to perform the simulation
and observe the property or phenomena of interest. It is important
to read and familiarize yourself with publications by other
researchers on similar systems. Choices of tools include:
- software with which to perform the simulation (consideration of
force field may influence this decision)
- the force field, which describes how the particles within the
system interact with each other. Select one that is appropriate
for the system being studied and the property or phenomena of
interest. This is a very important and non-trivial step! Consider
now how you will analyze your simulation data to make your
observations.
3. Obtain or generate the initial coordinate file for each molecule to
be placed within the system. Many different software packages are
able to build molecular structures and assemble them into suitable
configurations.
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. Several non-|Gromacs|
tools are useful here; within |Gromacs| :ref:`gmx solvate`,
:ref:`gmx insert-molecules` and :ref:`gmx genconf` solve frequent
problems.
5. Obtain or generate the topology file for the system, using (for
example) :ref:`gmx pdb2gmx`, :ref:`gmx x2top`, `SwissParam
<http://swissparam.ch/>`_ (for CHARMM forcefield), `PRODRG
<http://davapc1.bioch.dundee.ac.uk/cgi-bin/prodrg>`_ (for GROMOS96
43A1), `Automated Topology Builder
<https://atb.uq.edu.au/>`_ (for GROMOS96 53A6),
`MKTOP <http://www.aribeiro.net.br/mktop>`_ (for OPLS/AA) or your
favourite text editor in concert with chapter 5 of the |Gromacs|
`Reference Manual`_. For the AMBER force fields, `antechamber
<https://ambermd.org/antechamber/antechamber.html>`__ or
`acpype <https://github.com/alanwilter/acpype>`__
might be appropriate.
6. Describe a simulation box (e.g. using :ref:`gmx editconf`) whose
size is appropriate for the eventual density you would like, fill
it with solvent (e.g. using :ref:`gmx solvate`), and add any
counter-ions needed to neutralize the system (e.g. using :ref:`gmx
grompp` and :ref:`gmx insert-molecules`). 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 :ref:`gmx grompp`
and :ref:`gmx 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 :ref:`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. NVT, NVE). If you have problems here with the system :ref:`blowing
up <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 :ref:`gmx grompp` and
:ref:`gmx mdrun`, then :ref:`gmx energy` and :doc:`/how-to/visualize`).
10. Select the appropriate simulation parameters for the production
simulation (defined in :ref:`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 or phenomena of interest.
.. _Reference Manual: `gmx-manual-parent-dir`_
Tips and tricks
---------------
Database files
^^^^^^^^^^^^^^
The ``share/top`` directory of a |Gromacs| installation contains
numerous plain-text helper files with the ``.dat`` file extension.
Some of the command-line tools (see :doc:`cmdline`) refer to these,
and each tool documents which files it uses, and how they are used.
If you need to modify these files (e.g. to introduce new atom types
with VDW radii into ``vdwradii.dat``), you can copy the file from your
installation directory into your working directory, and the |Gromacs|
tools will automatically load the copy from your working directory
rather than the standard one. To suppress all the standard
definitions, use an empty file in the working directory.