An automatic generator of OPLS-AA force-field parameters for organic molecules and ligands — bond, angle, dihedral and Lennard-Jones terms with 1.14*CM1A or 1.14*CM1A-LBCC partial charges, ready for the major molecular-dynamics packages.
Powered by BOSS — the group's Monte Carlo engine does the work behind this form.
Before you can simulate a small molecule — a drug candidate, a ligand, a solvent — a computer needs its full force field: the numbers describing how each of its atoms bonds, bends, twists, and interacts with everything around it. Working those out by hand is slow and easy to get wrong.
LigParGen puts that job one paste away. Give it a molecule — as a SMILES string or a structure file — and it hands the work to BOSS, the group’s simulation engine, which assigns the OPLS-AA atom types and computes the CM1A partial charges. LigParGen then writes what comes back out as a complete parameter set — every bonded term included — formatted for GROMACS, OpenMM, CHARMM and seven more packages.
That convenience is why LigParGen is cited in well over a thousand studies — it turns a fiddly, error-prone setup step into a few seconds.
| BOSS Quick Start | TIP3P, TIP4P & TIP5P | Organic Solvents | LigParGen this page | |
|---|---|---|---|---|
| It answers | What shape does my molecule take, and how does it behave in water? | How do I get my molecule into a box of water, ready to simulate? | How do I get my molecule into an organic solvent? | What numbers does my MD program need for this molecule? |
| You get | The most stable shape, hydration free energy, dipole, surface area | Your molecule in thousands of water molecules, with ions, relaxed by BOSS | Your molecule in 512 solvent molecules, relaxed by BOSS | Force-field parameters |
| Files for | Docking, quantum chemistry, viewing | GROMACS, OpenMM, LAMMPS, AMBER, BOSS — ready to run | BOSS, GROMACS, OpenMM, LAMMPS — ready to run | GROMACS, OpenMM, CHARMM and 7 more |
| Solvent | Continuum water (GB/SA) | Real water molecules | Seven organic solvents | None |
| Time | Seconds to a few minutes | A few minutes | A few minutes | A few seconds |
Find your molecule’s best shape with BOSS Quick Start → put it in water on TIP3P, TIP4P & TIP5P, or in another solvent on Organic Solvents — or take only its force field here.
A structure with nothing but monatomic ions, such as lithium chloride, passed the check and then stopped with an error that didn't explain why. It is now flagged before the run: LigParGen parameterizes molecules, so use your force field's standard ion parameters for each ion.
BOSS's charge calculation handles at most 250 atoms, hydrogens included. Larger molecules, such as long alkane chains (C83H168 and up), passed the size check and then stopped with “'NoneType' object has no attribute 'group'”. They are now flagged before the run, with how to split the molecule into fragments that fit.
Molecules of only two atoms stopped with “IndexError: list index out of range”. OPLS-AA atom types are not built for them: when we made them run, no bond was written and CO's carbon was typed as an alkane carbon. They are now flagged before the run, with what to use instead: a model made for small gas molecules (such as TraPPE's for N2 and O2), or Cl- and Br- ion parameters for HCl and HBr in water.
A SMILES copied from a polymer repeat unit, such as *CC*, has open ends marked *, and the run stopped with an error. It is now flagged before the run, with how to fix it: cap each * with a hydrogen or a methyl group (*CC* becomes CCCC), or for a polymer use a capped trimer.
Structures saved from a drawing program with their hydrogens left implicit stopped with an error ending in “'NoneType' object has no attribute 'group'”. They are now flagged before the run, with how to fix it: enter the molecule as SMILES or save it with explicit hydrogens.
Borane and carborane cages were rejected with “This file could not be read”, which suggested re-exporting the file might help. They are now recognised and the page explains why LigParGen cannot parameterize them: cage atoms are bonded to five or six neighbours, which OPLS-AA atom types do not describe.
Flat 2D structures, such as PubChem's 2D SDF or a drawing program's export, can place unbonded atoms closer together than a bond. LigParGen then joins them and the run stopped with “'NoneType' object has no attribute 'group'” or “ERROR in atom order”. These files are now flagged before the run: upload a 3D structure (PubChem's 3D conformer SDF works) or enter the molecule as SMILES.
Some larger molecules, such as alkylthiophene oligomers, stopped with “invalid literal for int() with base 10: 'are'” because a note BOSS writes among its torsion parameters was read as data. They now run normally.
A file with many molecules, such as a box built with Packmol, was rejected with “This file could not be read”. The page now says how many separate molecules the file holds and to submit one molecule, or a capped repeat unit for a polymer.
Ions such as perchlorate, chlorate, bromate and periodate stopped with an error ending in “has no attribute 'GetBonds'”. OPLS-AA has no atom types for a halogen with more than one bond, so they are now refused before the run with a clear message and a pointer to published ion parameters.
Neutral amino acids labelled as standard residues (MET, GLY, …) with the acid hydrogen on the atom named O stopped with an error ending in “has no attribute 'GetBonds'”. They now run normally.
Files with more than one molecule, atoms missing a bonded partner, an odd electron count, elements BOSS cannot type, or too many atoms are now flagged under the file in about a second, all at once and with how to fix each, instead of failing after the run.
Molecules with a linear group, such as benzonitrile, acetonitrile or phenylacetylene, failed with two or more optimization rounds, and a structure drawn with an exactly 180° angle could run until it timed out. They now run normally.
PDB files that use HETATM rather than ATOM records are now accepted, and a run that would have returned all-zero charges is stopped with an explanation.
If a run failed for you and your problem is listed here, please run it again.
Citation count from Google Scholar, October 2026. Map from the peer-reviewed research citing LigParGen (doi:10.1093/nar/gkx312; via OpenAlex).
Dodda, L. S.; Cabeza de Vaca, I.; Tirado-Rives, J.; Jorgensen, W. L. LigParGen Web Server: An Automatic OPLS-AA Parameter Generator for Organic Ligands. Nucleic Acids Res. 2017, 45, W331–W336. doi:10.1093/nar/gkx312
Jorgensen, W. L.; Tirado-Rives, J. Molecular Modeling of Organic and Biomolecular Systems Using BOSS and MCPRO. J. Comput. Chem. 2005, 26, 1689–1700. doi:10.1002/jcc.20297