Preparing a coarse-grained (CG) model for molecular dynamics can look deceptively straightforward: load the structure, add water, and continue to simulation. But a setting that may be reasonable for an atomistic system can be too small for coarse-grained beads. The result can be solvent placed too close to the solute, creating clashes or an unsuitable solvent arrangement before the simulation even begins.
This walkthrough focuses on a practical detail that is easy to miss when preparing a CG system in GROMACS Wizard: checking the van der Waals distance used during solvation. The example follows a soluble MARTINI 3.0.0 protein, but the preparation logic is useful whenever you are setting up a CG model.
Start with a complete input folder
Before opening the preparation controls, make sure the CG structure and topology files are available together. In GROMACS Wizard, select Prepare, set the input source to Folder, and browse to the folder containing the model. For a model generated with Martinize2, this is the output folder containing files such as *_CG.pdb and *_CG.top, along with relevant .itp files.
After selecting the folder, check the detected PDB, TOP, and ITP files. Then click Load beside the PDB. Loading the structure is needed to compute the periodic box; it also gives you an opportunity to inspect the model before adding solvent.
Check the force field before adding solvent
For a model prepared with Martinize2 for MARTINI v.3.0.0, GROMACS Wizard should switch to the bundled martini_v.3.0.0 force field and set the default Martini water model. Confirm that the expected force field is selected rather than assuming the automatic choice is correct. If your CG model uses a different force field, provide that force field as part of the setup instead of proceeding with an incompatible one.
Next, decide whether the system needs solvent. If it does, enable Add solvent and open its options. This is where an important CG-specific adjustment lives.
Why the default solvent distance may be too small
Increase the default van der Waals distance to, for example, 0.21 nm. GROMACS does not have van der Waals distances defined for CG models in this context, so it uses its default value of 0.105 nm. That distance may be too small for CG beads. In the MARTINI model, one water bead represents four water molecules, so the bead is not equivalent in size to a single atomistic water molecule.
The practical takeaway is simple: do not treat the default distance as a universal value. For the MARTINI example, use a larger distance such as 0.21 nm, then leave the other solvent options at their defaults unless your model or workflow calls for a custom solvent model.
Set the box and ions in the right order
Review the periodic box size before preparing the system. The solute-box distance should be at least 1 nm to ensure the minimum distance between periodic images. You can also select a rhombic dodecahedron, a compact, space-filling unit-cell option, if it suits your setup.
If you need to neutralize the system or add salt, select the positive and negative ions and specify any additional salt concentration parameters. One dependency is easy to overlook: ions are added by replacing solvent molecules, so the option to add solvent must be enabled for ion addition. If there is no solvent to replace, the ion step cannot be performed as intended.
Prepare, inspect, then continue
Once the input files, force field, solvent distance, box, and ion settings are checked, click Prepare. You can load the prepared structure and inspect it before moving on. SAMSON can display detected CG systems as connected beads, with water shown in blue and ion beads colored using CPK colors for their corresponding atoms.
After verifying the prepared system, continue to minimization. In the Minimize tab, use the auto-fill button to set the previous preparation result as the input structure. If the topology contains position-restraint definitions, GROMACS Wizard can populate the corresponding preprocessing options. For Martinize2-generated restraints, check which restraint records are present and how they correspond to molecules before applying them during minimization or equilibration.
Quick preflight: confirm the correct CG force field; load the PDB so the periodic box is computed; increase the MARTINI solvent van der Waals distance from the default 0.105 nm to around 0.21 nm; keep the solute at least 1 nm from periodic images; and enable solvent if you plan to add ions. These checks help catch setup issues before beginning the simulation stages.
For the full workflow and interface details, see the GROMACS Wizard coarse-grained systems tutorial.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON at samson-connect.net.