Parametrization

MDFactory supports two force field parametrization methods for generating molecular mechanics parameters from SMILES strings. Both generate GROMACS-compatible ITP files.

Available parametrization methods

SMIRNOFF (OpenFF)

The SMIRNOFF parametrization uses the Open Force Field ecosystem to generate parameters. This is the recommended method for most applications.

Advantages:

• Modern, well-maintained force field (OpenFF 2.x "Sage")
• Automatic atom typing from SMILES
• Fast neural network-based partial charge assignment (NAGL)
• No external license required
• Parameters embedded directly in ITP files

Configuration:

engine: gromacs
parametrization: smirnoff
parametrization_config:
  forcefield: openff-2.2.0.offxml
  water_model: opc3.offxml
  charge_method: openff-gnn-am1bcc-0.1.0-rc.3.pt

Configuration options

Charge methods

parametrization_config:
  charge_method: openff-gnn-am1bcc-0.1.0-rc.3.pt

parametrization_config:
  charge_method: nagl

parametrization_config:
  charge_method: am1bcc

parametrization_config:
  charge_method: am1bccelf10

CGenFF

The CGenFF (CHARMM General Force Field) parametrization uses the CGenFF program to generate CHARMM36-compatible parameters.

Advantages:

• Well-validated for drug-like molecules
• Compatible with CHARMM36 lipid and protein force fields
• Extensive validation data available

Requirements:

• CGenFF license and installation (configure SILCSBIODIR in config.ini)

Configuration:

engine: gromacs
parametrization: cgenff

CGenFF does not require additional configuration options as it uses the global installation settings.

Choosing a parametrization method

Parameter caching

MDFactory automatically caches generated parameters to avoid redundant calculations:

~/.mdfactory/parameters/
└── gromacs/
    ├── cgenff/
    │   └── {molecule_hash}/
    │       ├── {hash}.itp
    │       └── {hash}_extra_params.itp
    └── smirnoff/
        └── {ff_config_hash}/
            └── {molecule_hash}/
                └── {hash}.itp

Parameters are cached by:

• MD engine (gromacs)
• Parametrization method (cgenff or smirnoff)
• Force field configuration hash (for SMIRNOFF — includes forcefield, water model, and charge method)
• Molecule hash (derived from canonical SMILES)

Parameter set structure

Each parametrized molecule produces a GromacsSingleMoleculeParameterSet containing:

Special molecules

Water

Water is handled specially by both parametrization methods:

• SMIRNOFF: Uses the configured water model (default: OPC3)
• CGenFF: Uses TIP3P from CHARMM36

Ions

Currently supported ions:

• Sodium: [Na+]
• Chloride: [Cl-]

Ions use formal charges and standard ion parameters from the respective force fields.

Troubleshooting

SMIRNOFF issues

"No conformer available"

The molecule needs a 3D conformer for charge assignment. This is handled automatically during parametrization, but may fail for very large or unusual molecules.

"Unsupported atom type"

Some exotic atoms may not be covered by OpenFF. Check the OpenFF coverage.

CGenFF issues

"SILCSBIODIR not set"

Configure the CGenFF installation path in config.ini:

[cgenff]
SILCSBIODIR = /path/to/silcsbio

High penalty scores

CGenFF penalty scores indicate parameter quality. Scores > 50 may indicate unreliable parameters.

Next steps