STaGE3 is the automatic GROMACS Topology Generation tool of small organic molecules using the GAFF and CGenFF
force fields with receptor system such as proteins or macro molecules.
STaGE3 is the python 3 fork of STaGE (https://gitlab.com/gromacs/stage) with some update improving usability.
If you use STaGE3, please cite original paper: Lundborg M., Lindahl E. Automatic GROMACS TopologyGeneration
and Comparisons of Force Fields for Solvation Free Energy Calculations. J. Phys. Chem. B. 2014, DOI: 10.1021/jp505332p
GNU GPLv3
You can try tutorial of STaGE3 to know how to install and run:
https://colab.research.google.com/github/mkatouda/stage3/blob/main/stage3_tutorial_jp.ipynb
STaGE3 also depends on a number of other softwares, some of which can should be installed seperately. They are:
- Required
- AmberTools (https://ambermd.org/AmberTools.php )
- acpype (https://alanwilter.github.io/acpype/)
- openbabel (http://openbabel.org/wiki/Main_Page)
- gromacs (https://www.gromacs.org/)
- Optional
- MATCH (available after filling in form at http://brooks.chem.lsa.umich.edu/index.php?page=registerSoftware&subdir=articles/resources/software&link=%3Ca%20href=%22downloads/MATCH_RELEASE.tar.gz%22%3EVersion%201.000%3C/a%3E&name=MATCH )
- Amsol (available after filling in form at http://t1.chem.umn.edu/license/form-user.html )
- Gaussian 16 or Gaussian 09 (https://gaussian.com/gaussian16/)
- Create conda virtual environment
conda create -n py38-stage3 python=3.8
conda activate py38-stage3
- Run the following command to install required conda packages
conda install -c conda-forge numpy ambertools acpype openbabel gromacs
- Install STaGE3 from github
pip install git+https://github.com/mkatouda/stage3.git
- Install STaGE3 from local repository
git clone https://github.com/mkatouda/stage3.git
cd stage3
pip install .
- Resiter and download MATCH program from offical web cite and extract archive file
tar xzvf MATCH_RELEASE.tar.gz
- Set up enviroment variables for MATCH
export PerlChemistry=/path/to/MATCH_RELEASE/PerlChemistry
export MATCH=${HOME}/path/to/MATCH_RELEASE/MATCH
export PATH=${PATH}:${MATCH}/scripts
usage: stage3 [-h] [-i INP] [-l LIGAND] [-s SMILES] [-o OUTPUT] [--ffligand FFLIGAND]
[--ffprotein FFPROTEIN] [-x CALIBRATION] [-k] [-p PH] [-r]
[-q CHARGE_METHOD] [-f CHARGE_MULTIPLIER] [-c MERGECOORDINATES]
[-t MERGETOPOLOGY] [-b BOX_TYPE] [-d BOX_BUFFER] [-w WATER]
[--conc CONC] [--pname PNAME] [--nname NNAME] [-v]
optional arguments:
-h, --help show this help message and exit
-i INP, --inp INP yaml style input file, overwriting argument values (default: None)
-l LIGAND, --ligand LIGAND
ligand (PDBQT, MOL, SDF, MOL2, PDB) (default: None)
-s SMILES, --smiles SMILES
Use the specified smiles string as input instead of an input file
(must be inside quotes). (default: None)
-o OUTPUT, --output OUTPUT
Name of the output files (file extensions will be appended).
(default: None)
--ffligand FFLIGAND Force fields to generate parameters for, specified as
a comma-separated string without spaces:
gaff, gaff2, cgenff (default: gaff)
--ffprotein FFPROTEIN
Force field of protein. (default: None)
-x CALIBRATION, --calibration CALIBRATION
Modify van der Waals parameters according to specified calibration
file. (default: None)
-k, --keep_ligand_name
Do not rename the ligand in the output files. When doing
e.g. solvation or binding free energy it is convenient
to always call the ligand the same thing - in this case "LIG".
If this option is set the ligand name will not be changed to "LIG".
If you need to assign parameters to e.g. co-factors it is good
to keep their names to tell them apart from ligands. (default: False)
-p PH, --ph PH Protonate the molecule according to this pH (float).
This does not always give correct results.
It is safer to provide correctly protonated input files. (default: None)
-r, --retain_charges Keep the mol2 charges. (default: False)
-q CHARGE_METHOD, --charge_method CHARGE_METHOD
Use the specified charge method for all force fields.
am1bcc: AM1 with bond charge correction (antechamber)
am1bcc-pol: STaGE's own more polarized bond charge correction (antechamber)
mmff94: MMFF94 (Open Babel)
eem: electronegativity equalization method (Open Babel)
qeq: Assign QEq (charge equilibration) partial charges (Rappe and Goddard, 1991) (Open Babel)
qtpie: Assign QTPIE (charge transfer, polarization and equilibration) partial charges (Chen and Martinez, 2007) (Open Babel)
gaussian/hf: Hatree-Fock/6-31G(d) basis set followed by RESP (Gaussian)
(default: am1bcc)
-q CHARGE_METHOD, --charge_method CHARGE_METHOD
Use the specified charge method for all force fields. (default: am1bcc)
-f CHARGE_MULTIPLIER, --charge_multiplier CHARGE_MULTIPLIER
Multiply partial charges with this factor. Can only be used
in combination with --charge_method. (default: 1.0)
-c MERGECOORDINATES, --mergecoordinates MERGECOORDINATES
Merge the created coordinates file (.gro) with an already
existing coordinate file (.pdb or .gro), e.g. for combining ligand
coordinates with protein coordinates. The generated
topology will contain both the ligand and the protein.
If a .gro file of the protein is provided and there exists
a corresponding .top file that toplogy file will be used for
the protein, otherwise a new topology file is generated. (default: None)
-t MERGETOPOLOGY, --mergetopology MERGETOPOLOGY
Merge the created topology file (.top) with an already existing
topology file. Must be used in combination with --mergecoordinates
with a .gro file of the protein. (default: None)
-b BOX_TYPE, --box_type BOX_TYPE
Type of simulation box: triclinic, cubic, dodecahedron, octahedron
(default: dodecahedron)
-d BOX_BUFFER, --box_buffer BOX_BUFFER
Buffer from the solute to the edge of the solvent box.
Set to 0 to disable solvation (and ionisation). (default: 1.0)
-w WATER, --water WATER
Solvent model to use in topology files. If not specified
the solvent will not be specified in the topology.
Suggested water models are:
opc, spce, tip4pew, spc, tip3p (default: None)
--conc CONC Specify salt concentration (mol/liter). (default: 0.0)
--pname PNAME Name of the positive counter ion in Solvent. (default: NA)
--nname NNAME Name of the negative counter ion in Solvent. (default: CL)
-v, --verbose Verbose output. (default: False)
Generates MD input files for ethanol using mol file as input for all available force fields using the default charge methods.
stage3 -l ethanol.mol -o ethanol
Generates MD input files for ethanol using a mol2 file as input and retaining all the partial charges that were specified in the mol2 file.
stage3 -i ethanol.mol2 -o ethanol -r
Generates MD input files for water solvated ethanol using mol file as input.
GAFF with Hatree-Fock 6-31G* charge method, which runs Gaussian to calculate the charges and can take a long time, is used.
Mininum distance of 1.2 nm from the solute to the edge of the dodecahedron periodic box. TIP3P water model is used.
stage3 -l ethanol.mol -o ethanol_solvated --ffligand gaff -q gaussian/hf -w tip3p -b dodecahedron -d 1.2
Generates MD input files for water solvated protein-ligand complex using protein pdb file and ligand mol file as input.
GAFF2 with AM1-BCC charge method and AMBER99SB-ILDN force fields are used for ligand and protein, respectively.
Mininum distance of 1.0 nm from the solute to the edge of the cubic periodic box.
TIP3P water model is used and the system is neutralized adding charged counter ions (K+) or (Cl-).
stage3 -l ligand.mol -c protein.pdb -o protein_ligand_solvated --ffligand gaff2 -q am1bcc --ffprotein charmm27 \
-w tip3p -b cubic -d 1.0 --pname K --nname CL
Generates MD input files for water solvated protein-ligand complex using protein pdb file and ligand mol file as input.
GAFF2 with AM1-BCC charge method and AMBER99SB-ILDN force fields are used for ligand and protein, respectively.
Mininum distance of 1.0 nm from the solute to the edge of the cubic periodic box.
Prepare input yaml file input.yml:
ligand: './jz4.mol'
mergecoordinates: './3HTB_protein.pdb'
output: '3HTB-jz4-wat'
ffligand: 'gaff'
ffprotein: 'amber99sb-ildn'
charge_method: 'am1bcc'
water: 'tip3p'
box_type: 'dodecahedron'
box_buff: 1.0
conc: 0.1
pname: 'NA'
nname: 'CL'
verbose: True
Then, run stage3 in command line:
stage3 -i input.yml
Keywards of yaml file are the same in the name of command line options.
See above explanation of command line options.
Michio Katouda ([email protected])