[gmx-users] The Futility of Validating OPLS Parameters for an Organic Cation

[Chris Ing]

Hello,
 Frequent MD simulator, first time parameterizer. I'm interested in
validating my parameters for the organic cation NMDG+ for OPLS/AA. The
molecule itself isn't that complicated (
http://www.chemspider.com/Chemical-Structure.8249.html) and I'm quite
confident that all the atom types are in OPLS/AA. I've made models using
the standard OPLS charges for each atom type and several point charge
assignment protocols with Gaussian/RESP consistent with OPLS. I've done
explicit water simulations with those in Gromacs, which look fine, but now
I'm stumped about how to verify my parameters.

 Experimental heats of vaporization and density seem to be common metrics
of validation for force field parameters.  OPLS parameters were tested
against those properties for various ionic liquids (1) and again for a
large number of neutral molecules (2). Unfortunately, I have no
experimental data for an ionic liquid containing NMDG+.

 Validating my parameters with only theoretical methods "initially" seemed
like a good choice. I calculated the free energy of solvation for my
molecule in Gaussian, with implicit solvent, but as I understand it, it's
either not possible or very difficult (with a boundary correction, 3) to do
free energy perturbation with a charged molecule. This is a topic which is
frequently addressed by David Mobley on this mailing list:
http://lists.gromacs.org/pipermail/gmx-users/2006-March/020672.html
http://lists.gromacs.org/pipermail/gmx-users/2006-September/023942.html
http://lists.gromacs.org/pipermail/gmx-users/2009-December/047455.html
http://lists.gromacs.org/pipermail/gmx-users/2011-August/063843.html

 Would the best solution be to contact an experimentalist who studies ionic
liquids containing my cation (4) to request experimental data or is there
something I'm missing?

-Christopher Ing
University of Toronto


1. Sambasivarao, S.V., Acevedo, O.: Development of OPLS-AA Force Field
Parameters for 68 Unique Ionic Liquids. J. Chem. Theory Comput. 5,
1038–1050 (2009).

2. Caleman, C., van Maaren, P.J., Hong, M., Hub, J.S., Costa, L.T., van der
Spoel, D.: Force Field Benchmark of Organic Liquids: Density, Enthalpy of
Vaporization, Heat Capacities, Surface Tension, Isothermal Compressibility,
Volumetric Expansion Coefficient, and Dielectric Constant. J. Chem. Theory
Comput. 8, 61–74 (2012).

3. Kastenholz, M.A., Hünenberger, P.H.: Computation of
methodology-independent ionic solvation free energies from molecular
simulations. II. The hydration free energy of the sodium cation. J. Chem.
Phys. 124, 224501 (2006).

4. Joshi, M.D., Chalumot, G., Kim, Y.-W., Anderson, J.L.: Synthesis of
glucaminium-based ionic liquids and their application in the removal of
boron from water. Chem. Commun. 48, 1410 (2012).