We are happy to announce the availability of the ParamChem website at https://www.paramchem.org/ . The current implementation of ParamChem features the CHARMM General Force Field (CGenFF) program for automatic atom typing and assignment of parameters and charges by analogy. The utility is based on CGenFF, the extension of the CHARMM additive force field that allows for the treatment of drug-like compounds, and allows users to upload molecules in MOL2 format from which a CHARMM compatible RTF of the molecule, including charges, is created along with parameters that supplement CGenFF as required for the molecule. Note that penalty scores are assigned to each charge and parameter produced by the CGenFF program, allowing users to gauge the quality of the generated parameters. However, given the limited transferability of empirical force fields, even parameters with small penality scores may not be optimal and validation of the parameters, as described in the CGenFF manuscript, is highly suggested. Efforts to develop more automated methods for parameter validation are ongoing as part of the ParamChem effort.
We hope you find the ParamChem/CGenFF combination of utility. Details of how to use ParamChem are below.
Alex, Kenno and the entire ParamChem team ( https://www.paramchem.org/AboutUs.html )
- 1) Register at https://www.paramchem.org/Registration/index.php . You will receive an e-mail with information on how to activate your account. Presently, only academic and government users are allowed.
- 2) Upload your molecule of interest in mol2 format at https://www.paramchem.org/AtomTyping/index.php . It is important that all hydrogens are present, in the correct protonation and tautomeric states, and that the connectivity is correct. The xyz coordinates are not critical. The maximum number of atoms is 256, and there is a limit of 100 molecules per user per week. Note that CGenFF should not be used for biological macromolecules; see the notes on the main CGenFF page or the FAQ for details. The highly optimized CHARMM force field for Proteins, Nucleic Acids, Carbohydrates and Lipids can be downloaded freely from the CHARMM force field page and can readily be combined with CGenFF.
- 3) 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.
- 4) 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.
- 5) The stream file produced by the CGenFF program represents an extension of the main CGenFF topology and parameter files, which can be downloaded here. 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! At the time of writing, the available version of the CGenFF program is 0.9.0, which requires the latest version of the CGenFF force field, 2b6.
- 6) Congratulations, you're ready to run CHARMM. Here's a basic example showing how to run an energy minimization.
Note: Both CGenFF and the functionality exposed through this interface ("the CGenFF program") are in beta stage of development. Although extensive testing has been performed during the alpha stage, we are not responsible for potential problems although we will certainly attempt to address issues associated with problems via email to firstname.lastname@example.org. The CGenFF force field and program will be updated in tandem at regular dates. These updates will increase the number of supported chemical groups, but may also lead to small changes in the charges and parameters assigned to a given molecule. Therefore, when citing CGenFF/Paramchem, it is important to include the version number of the interface (0.9.0 at the time of writing) and the force field (2b6 at the time of writing).
Cite CGenFF/ParamChem respectively as
- CGenFF: K. Vanommeslaeghe, E. Hatcher, C. Acharya, S. Kundu, S. Zhong, J. Shim, E. Darian, O. Guvench, P. Lopes, I. Vorobyov, A. D. MacKerell Jr., J. Comput. Chem. 2010, 31, 671-690.
- Atom typing and assignment of parameters and charges by analogy: K. Vanommeslaeghe et al, in preparation.
- ParamChem interface: www.paramchem.org