The box is part of the model: avoid periodic-image artifacts before you run

A molecular system can look perfectly prepared and still have a box that is too small. With periodic boundary conditions, the simulation repeats the system in every direction. If the solute is too close to its own periodic copy, it may interact with that copy—and the resulting forces can be wrong. Box design is therefore more than a setup detail: it is one of the checks that helps protect a simulation from avoidable artifacts.

Here is a practical way to think through the choice: first decide how much space the solute needs, then choose a box shape that uses that space sensibly, and finally check the distance between periodic images.

What periodic boundaries mean in practice

Under periodic boundary conditions, the simulation cell is surrounded by copies of itself. For short-range non-bonded interactions, GROMACS uses the minimum image convention: it considers the nearest image of each particle. Long-range electrostatics require additional methods, such as Ewald summation or PME; periodic boundaries do not make those interactions equivalent to short-range ones.

The key setup concern is that the solute should not interact with its own periodic image. A useful rule of thumb is to leave at least 1.0 nm between the solute and the box boundary. That gives at least 2.0 nm between periodic images of the solute. Treat this as a practical starting point, not a replacement for checking the cutoff restrictions that apply to your simulation.

Choose a shape that fits the solute

GROMACS Wizard supports cubic, orthorhombic, triclinic, rhombic dodecahedron, and truncated octahedron unit cells. The right choice depends on the shape of your system and how much solvent the box needs to contain.

For an approximately spherical macromolecule in solution, a cube may leave more unused space than necessary. A rhombic dodecahedron or truncated octahedron is closer to a sphere, so it can require fewer solvent molecules while maintaining a given distance between periodic images.

Rhombic dodecahedron unit cell — A rhombic dodecahedron is one option for reducing unused space around an approximately spherical solute.

The rhombic dodecahedron is the smallest and most regular space-filling unit cell described in the documentation. At the same image distance, its volume is 71% of the volume of a cube—about 29% less. That can mean fewer solvent molecules and less simulation work for a spherical or flexible molecule in solvent. It is a useful efficiency consideration, not a reason to ignore the required image distance.

Truncated octahedron unit cell — The truncated octahedron is another sphere-like option available in GROMACS Wizard.

Two ways to set the initial box

In GROMACS Wizard, you can start by specifying Box lengths or a Solute-box distance. These options solve slightly different setup problems:

Box lengths: The box is fitted tightly to the system. You then increase its size as needed to satisfy the minimum image convention. 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, so it is useful when you want one box size across the batch.
Solute-box distance: You specify the distance between the solute and the box. At least 1 nm is recommended as a practical way to provide room between periodic images. For a batch project, box sizes can differ for each conformation or path frame.

Choosing a unit cell and box settings during preparation — Choose the unit-cell shape and box sizing approach during system preparation.

A quick check before running

Ask whether the solute is roughly spherical; if it is, consider a rhombic dodecahedron or truncated octahedron.
Check whether the box leaves enough room between the solute and its periodic images. The documented 1 nm solute-to-boundary distance is a practical rule of thumb.
If using fixed box lengths, remember that the initial tight fit may need to be enlarged.
If preparing multiple conformations, consider whether you need one common box size or a box sized separately for each conformation.
Check the GROMACS cutoff restrictions for the simulation you intend to run.

One detail that can help when inspecting results: GROMACS keeps particles in a brick-shaped volume for efficiency. When importing GROMACS trajectories, SAMSON attempts to detect the unit-cell type, and the type can be adjusted in the importer dialog.

For the full explanation and related setup steps, see the GROMACS Wizard guide to periodic boundary conditions.

Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON.