CGenFF This page was originally developed by Kenno Vanommeslaeghe here. MacKerell Lab Computer-Aided Drug Design Center

University of Maryland, Baltimore Baltimore, MD 21201 USA

Contents

• Generating atom types, charges and parameters by analogy
• Running CHARMM simulations with the resulting parameters
  • Basic energy minimization
  • MD simulation in the presence of a protein and explicit water
  • Using CHARMM's Domain Decomposition (DOMDEC) or implicit solvents
• Running simulations with other programs
  • NAMD
  • ACEMD
  • GROMACS
  • Other programs
• How it works
• Acknowledgement

Generating atom types, charges and parameters by analogy

1. Register. You will receive an e-mail with information on how to activate your account. Presently, only academic and government users are allowed.
2. Create a mol2 file of your molecule, being careful that that all hydrogens are present, in the correct protonation and tautomeric states, and that the bond orders are correct. Unfortunately, there are few open source molecular editors that allow the user to visualize and edit bond orders and save the result as a valid mol2 file that is conform the mol2 standard. Here are 2 closed-source programs that are free of charge and allow you to do so:
   • Accelrys' Discovery Studio Visualizer
   • Schrödinger's Maestro (free for academia only through the Maestro Academic Campaign)
   Additionally, here are some non-free programs (other than the paid versions of the above):
   • Chemical Computing Group's MOE
   • Tripos' Sybyl
   • Semichem's AGUI (part of the AMPAC suite) after sed -i 's/Ar/ar/' *.mol2
   • Gaussian's GaussView after sed -i 's/Ar/ar/' *.mol2
   • Hypercube's HyperChem after sed -i 's/_\+ //' *.mol2
   Please email Kenno Vanommeslaeghe if you think additions should be made to these lists! In particular, it would be nice to know of an open-source program that has the same abilities.
   Note that mol2 files from the Zinc database are generally high-quality.
3. Upload the resulting mol2 file. Note that CGenFF should not be used for biological macromolecules; see the notes on the main page or the FAQ for details.
4. If the interface returns warnings, look at them carefully - warnings often imply that the parameters may not be sufficiently accurate for use without validation and/or optimization.
5. Download the str file and open it in a text viewer or editor. In particular, look at the "penalty scores" associated with the partial charges and parameters. Penalties between 10 and 50 indicate that some basic validation is recommended; penalties higher than 50 usually are usually associated with parameters or charges that need additional optimization. It should be noted that even in cases were the penalty score is low, the accuracy of the parameters cannot be 100% guaranteed. In all cases it is recommended that the user perform some level of validation of the parameters prior to use.
6. After validation and/or optimization of the high-penalty parameters and charges, the molecule is ready for MD simulations. Just remember that when writing a paper using CGenFF parameters, the versions of both the CGenFF force field and the CGenFF program should be mentioned in order to ensure reproducibility!

Running CHARMM simulations with the resulting parameters

Basic energy minimization

1. Download the main CGenFF topology and parameter files.
2. Verify that your stream file is compatible with the CGenFF version you downloaded (all the files contain comments with version information). Using incompatible files may not result in errors but may give rise to inconsistent energetics! If needed, older CGenFF versions can be found on the download page. (Currently, the available version of the CGenFF program is 1.0.0, which requires the latest version of the CGenFF force field, 3.0.1 .)
3. Rename your stream file to molecule.str and your mol2 file to molecule.mol2 , where molecule is the name of your molecule as found in the RESI line in your stream file.
4. Download the minimize.inp CHARMM script and the mol2crd shell script and save them in the same directory where your stream file and your CGenFF topology and parameters files are located.
5. Run the following commands:
   chmod 755 mol2crd    (this needs to be run only once)
   charmm resi=molecule -i minimize.inp -o molecule.out
6. If everything went well, molecule.out should have "NORMAL TERMINATION BY END OF FILE" somewhere in the last 20 lines. If not, go to the beginning of the file and search for occurrences of the word "WARNING". In 90% of cases, the first warning message is the cause of the problem.
7. If CHARMM finished successfully, the minimized structure is saved to molecule_min.pdb and molecule_min.crd . It is recommended to visualize this final geometry; if it is not reasonable, something may be wrong with the force field (although a bad minimized structure may also result from having an unreasonable geometry in the initial mol2 file, as reproduced in molecule_init.pdb and molecule_init.crd ). Note that a good minimized structure is not a guarantee that the force field is good enough for all purposes; in particular, a minimized structure in vacuum is of limited relevance for assessing intermolecular interactions.

MD simulation in the presence of a protein and explicit water

Using CHARMM's Domain Decomposition (DOMDEC) or implicit solvents

Running simulations with other programs

NAMD

1. Download and unpack the latest CHARMM force field distribution
2. Overwrite the main CGenFF topology and parameter files downladed in the previous step with the latest CGenFF version (the CGenFF program works only with the latest CGenFF release and CGenFF releases are often ahead of the releases of the CHARMM force field)
3. Download toppar_water_ions_namd.str and put it alongside the other parameter files
4. Generate the system of interest in CHARMM and write a PSF in XPLOR format
   - OR -
   Generate a PSF using VMD's psfgen plugin (note that we haven't tested this)
   - OR -
   Generate your system and its XPLOR PSF with CHARMM-GUI (yes, it does officially support NAMD)
5. ONLY FOR VERY OLD NAMD VERSIONS: edit the main CGenFF parameter file (ie. par_all36_cgenff.prm ) and remove the ATOMS section with MASS entries.
6. Read the XPLOR PSF and all the parameter files (plus the str file with molecule-specific parameters) into NAMD as follows:

   ...
   structure system-xplor.psf
   paraTypeCharmm on
   parameters par_all36_prot.prm
   mergeCrossterms yes
   parameters par_all36_lipid.prm
   parameters par_all36_carb.prm
   parameters par_all36_cgenff.prm
   parameters molecule.str
   parameters toppar_water_ions_namd.str
   ...

ACEMD

GROMACS

Other programs

How it works

Acknowledgement