A molecular system can look ready for simulation and still be poorly prepared. One common source of trouble is the periodic box: if it is too small, a molecule may interact with its periodic image. If solvent or ions are needed, they must also be added in a way that matches the model. These choices affect the system that later steps will minimize and simulate, so it is worth checking them before pressing Prepare.
This guide focuses on three practical decisions in GROMACS Wizard: choosing the solvent model, defining a suitable periodic box, and adding ions. The aim is not to prescribe one setup for every system, but to help you understand what each choice controls and what to check.
Start with a consistent model
First choose a force field appropriate for your system. Force-field selection matters because it can influence simulation results; consult the relevant publications and conventions for your system. The water models available in GROMACS Wizard depend on the selected force field. If you want explicit solvent, select a compatible water model and enable Add solvent. Selecting none as the water model means you cannot add solvent or ions.
If the system includes a ligand or another molecule for which GROMACS cannot generate a topology, provide its include topology file (.itp) and use the force field with which that molecule was parametrized. A topology and force field that do not match are not interchangeable setup details; check their provenance before continuing.
For the tutorial example, the chosen water model is SPC/E. The specific choice here is an example, not a universal recommendation.
Size the box around the system—not just the picture
GROMACS Wizard supports cubic, orthorhombic, triclinic, rhombic dodecahedron, and truncated octahedron unit cells. To create an initial box, select the system in the Document view, choose a cell type, and click Compute fitted box. The fitted box is based on the dimensions of the selected structure, so check that it includes every structure you intend to prepare.
There are two ways to set the fit:
- Solute-box distance sets a distance between the solute and the box. The documentation recommends at least 1 nm to help satisfy the minimum image convention. For a batch project, this option can produce a different box size for each conformation or trajectory frame.
- Box lengths lets you specify the box dimensions. The initial fit is tight, so increase the dimensions to leave enough space around the system. For a batch project, the initial size is based on all conformations or the full path, which can be useful when a consistent box size is wanted.
Why does this space matter? Under periodic boundary conditions, the simulation represents repeating copies of the box. The minimum image convention helps prevent a solute from interacting with its own periodic image. A distance of at least 1 nm from solute to box edge is recommended in the guide; that corresponds to at least 2 nm between periodic images. Because molecules can change conformation, consider the system’s possible shapes rather than only its starting appearance. Custom force fields may have specific requirements, so verify those as well.
After computing the fit, you can adjust the unit-cell parameters. Treat the displayed box as a starting point, not as proof that the spacing is adequate.
Add ions with their purpose in mind
Ions are added by replacing water molecules, so solvent must be enabled if you want to add ions. Check Neutralize system when the system needs counterions to bring its total charge to neutral. GROMACS determines which ion type to add from the system’s total charge. You can use Update to calculate that charge before running preparation. For example, a total charge of +8 calls for eight negative ions to neutralize it.
Neutralization and salt concentration are related but distinct choices. To add salt beyond the counterions, enable Add additional ions. You can specify a number of additional positive and negative ions, or a salt concentration. The documentation notes that specifying a concentration adds ions on top of neutralizing counterions; existing ions are not counted toward the specified concentration. A concentration of 0.15 M NaCl is cited as a popular representation of physiological conditions, but the appropriate setting depends on the intended system and study.
A quick preflight before preparation
- Confirm you selected the intended structure or structures.
- Check that the force field and any additional topology files belong together.
- Choose a compatible water model and enable solvent if you need solvent or ions.
- Verify that the box contains all selected structures and leaves appropriate solute-to-edge spacing.
- Decide whether you need neutralizing ions only or additional salt.
When these choices are set, click Prepare. GROMACS Wizard generates the model and adds solvent and ions when requested. Review any warnings and the output log; after preparation, the resulting structure can be imported into SAMSON for inspection.
For the complete workflow and further details, see the GROMACS Wizard preparation tutorial.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON.