A molecular system can look ready for simulation and still be missing a crucial piece: a suitable periodic box, compatible topology files, or the solvent and ions needed for the intended setup. These decisions are easy to treat as form-filling, but they affect what system is actually prepared. A little planning here can prevent avoidable setup problems later.
This guide focuses on a common modeling pain: turning a structure into a simulation-ready system without overlooking dependencies between the force field, solvent, box, and ions. The workflow below follows the preparation step in SAMSON’s GROMACS Wizard.
Start with the system you mean to simulate
In the Prepare step, choose the molecular system from the active document and click Set system. If the document contains multiple structural models, select the intended model or models first. Leaving the selection empty can prompt you to include all structural models, so take a moment to confirm what will be prepared.
This matters especially for batch work. A batch project can use multiple conformations or trajectory frames, or apply the same computation to different systems. If you plan to compare conformations or use a workflow such as umbrella sampling, decide early whether a batch project is appropriate. The box-fitting choice can affect whether the batch uses a shared box size or different box sizes for individual conformations.
Make force field and topology choices together
Choose a force field that is suitable for your system; the documentation emphasizes that force-field choice can significantly influence a simulation. If the system contains a ligand or another molecule that GROMACS cannot parameterize itself, provide its include topology file, typically an .itp file. The topology must be compatible with the force field used to parameterize that molecule. For example, if a topology came from ATB, the corresponding force field may also be needed.
In other words, do not treat an extra topology file as an isolated attachment. Check that you have the topology and its matching force-field requirements before preparation. For protein–ligand setups, consult the dedicated protein-ligand systems tutorial.
Choose solvent before planning ions
Select a water model provided by the chosen force field, or add a custom solvent model if necessary. To add explicit solvent, enable Add solvent. If you select none as the water model, you cannot add solvent or ions.
This dependency is important: GROMACS adds ions by replacing water molecules, so solvent must be present if you want to add ions. You can enable neutralization, choose the available positive and negative ion types, and optionally add more ions by specifying a number or salt concentration. A salt concentration of 0.15 M NaCl is noted in the documentation as a popular choice representing physiological conditions; it is a setup choice, not a universal requirement for every study.
Use the box option that matches your goal
The periodic box must contain all structures selected for preparation. GROMACS Wizard supports cubic, orthorhombic, triclinic, rhombic dodecahedron, and truncated octahedron unit cells. Two fitting approaches help you establish its dimensions:
- Solute-box distance: specify the spacing between the solute and box. The tutorial recommends at least 1 nm to help satisfy the minimum image convention. For a batch, this approach can produce different box sizes for different conformations or trajectory frames.
- Box lengths: specify the box dimensions. The fitted box is tight around the system, so increase its size to provide enough space. For a batch, the initial size is based on all conformations or the whole path, which can be useful when you want the same box size throughout.
The minimum image convention is a practical safeguard against a molecule interacting with its own periodic image. For box-length setups, the documentation recommends at least 1.0 nm between the system and box edges, corresponding to at least 2.0 nm between periodic images. Check the needs of your chosen force field and cutoff scheme, particularly when using a custom force field.
A quick pre-run checklist
- Confirm the intended model or models are selected.
- Check that any non-standard molecules have the required topology files and compatible force field.
- Choose a solvent model before enabling ion addition.
- Confirm the box contains every selected structure and has suitable spacing.
- Decide whether neutralization alone is needed or whether additional ions or a salt concentration are appropriate.
Once these choices are set, click Prepare. Review any pop-ups or warnings, and use the Output button to inspect the log if needed. After preparation, you can import the system into SAMSON and continue to energy minimization.
For the complete walkthrough and interface details, see the GROMACS Wizard preparation documentation.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON.