A molecular simulation box can look perfectly reasonable and still cause trouble: if the solute is too close to a boundary, periodic copies of the system may interact when you intended to study an isolated molecule in solution. Choosing a box is therefore more than a setup detail. It is a practical balance between avoiding unwanted interactions and not simulating more solvent than necessary.
Periodic boundary conditions make a finite box behave like a repeating space-filling arrangement. In GROMACS, the minimum image convention means that, for short-range non-bonded interactions, the nearest periodic image of a particle is considered. If the box is too small, a solute may effectively encounter its own periodic copy. The resulting forces can be misleading.
Start with the solute’s shape
GROMACS Wizard offers cubic, orthorhombic, triclinic, rhombic dodecahedron, and truncated octahedron unit cells. The best starting point depends on the system’s geometry. A cube is familiar and straightforward, but it can leave more unused space around an approximately spherical solute.
For a roughly spherical macromolecule in solvent, the rhombic dodecahedron and truncated octahedron can fit more efficiently. They are closer to spherical than a cube, so they can require fewer solvent molecules while maintaining a given distance between periodic images. The rhombic dodecahedron is the smallest and most regular space-filling unit cell described here: its volume is about 71% of a cube with the same image distance. In the right kind of system, that can mean less solvent to simulate.
A rhombic dodecahedron can reduce empty space around an approximately spherical solute.
That efficiency is not a reason to choose it automatically. Match the box to the system and the setup you need; a less spherical or elongated solute may call for a different shape or orientation. The key is to compare shapes while preserving enough clearance around the solute.
Use clearance as a safety check
A practical rule of thumb is to leave at least 1.0 nm between the solute and the box boundary. This gives at least 2.0 nm between periodic images of the solute. Treat this as a useful setup check, not a substitute for checking the cutoff restrictions and simulation settings relevant to your system. The exact constraints depend on the simulation parameters.
In GROMACS Wizard, there are two ways to define the initial box:
- Box lengths: specify the box dimensions. The initial fit is tight, so increase the size as needed to provide adequate clearance. This option also lets you move the box to position the system. For a batch project, the initial size is based on all conformations or the whole path, which is useful when you want one box size throughout.
- Solute-box distance: specify the distance from the solute to the box. At least 1 nm is recommended as a practical way to help satisfy the minimum image convention. In a batch project, each conformation or path frame gets its own box dimensions.
Choose the unit-cell shape and fitting approach as part of system preparation.
A quick setup checklist
- Consider whether the solute is approximately spherical or has a more elongated shape.
- Choose a suitable unit-cell shape, then check the solute’s clearance from the box boundaries.
- Use the 1 nm clearance rule as a practical starting point, and verify that your box is compatible with the relevant cutoff restrictions.
- For batch simulations, decide whether a shared box or per-conformation boxes better fit your workflow.
One detail can be surprising when inspecting results: GROMACS keeps particles in a brick-shaped volume for efficiency. When loading trajectories, SAMSON attempts to detect the unit-cell type, and you can adjust it in the importer dialog if needed.
For the full explanation of unit-cell shapes and minimum-image considerations, see the SAMSON documentation on periodic boundary conditions.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON.