[gmx-users] Validation of forcefield for small molecules

[Justin Lemkul]

On 3/4/19 1:23 AM, Hemalatha Jayabal wrote:
> Dear all,
> I am working on studying the effect of a molecule on a protein. I am using
> CHARMM force-field in GROMACS for a protein (From literature studies and
> validation of protein properties, this force field was chosen) and I intend
> to study the effect of a molecule on the protein. The molecule taken was
> L-Ascorbic acid and I obtained the structure of the file through ZINC
> database, CSD and RCSB ligand database (Tried all 3 structures) . I
> obtained the topology files for CHARMM using (a) SWISSPDB (b) LigParGen and
> (c) ParamChem.org (Gives high penalties , hence I did not use this

Penalties in what? Charges? Dihedrals? I imagine the nonbonded 
parameters should be relatively easy to assign for this molecule, though 
you may get some dihedral problems from the ring. But those shouldn't be 
hard to sort out.

> topology). In order to validate the force-field of this structure, I took a
> box of roughly 2000 molecules (L-Ascorbic acid) and ran a equilibriation,
> NVT and NPT (20ns). But, I am unable to obtain the desired density of the
> compound (Reported in literature = 1.65 g/cm3) , obtained density from my
> MD studies (1.48 g/cm3).
>
> I have tried obtaining charges through semi-empirical DFT and used those
> charges as well. But I cannot obtain the density of the compound. This
> molecule exists as solid at the given conditions (P= 1 atm, T= 298 K).
> Should I look at any other property of the compound? If so, what properties
> could be validated for solids?
>
> I am aware that parametrization of a molecule is a tedious process. Should
> I go forward and try doing that? Or are there any more parameters or
> conditions that I have failed to look at?
>

CGenFF tells you where the potential problems are, and the method for 
tuning the parameters is published and very robust, provided you can do 
the parameter fitting (there are also programs to do this for dihedrals).

-Justin


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Justin A. Lemkul, Ph.D.
Assistant Professor
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