Re: Protein-ligand simulation

From: Kenno Vanommeslaeghe (
Date: Tue Jun 25 2013 - 14:17:17 CDT

Hi James,

On 06/25/2013 02:39 PM, James Starlight wrote:
> Kenno,
> thank you again for such detailed explanations!
> Unfortunately I didnt find parameters for cyclic nucleotides in the
> charm27 param files (I've looked for it in the par_all27_na.prm and
> par_all27_na.inp ) Perhaps I should look for the PRES CY35entry in the
> latest charm 36 ff but I'm not sure if it reasonable to mix 27 parameters
> ( for protein) and 36 for ligand.

- Yes, I was looking at the CHARMM36 NA force field.
- Technically spoken, cyclic nucleotides don't need special parameters,
though chemically spoken, the use of the non-cyclic parameters must be
validated. The presence of the intra-nucleotide cyclization patch in
CHARMM36 suggests that's been done (for CHARMM36 at least).
- I don't think it would be a huge problem to mix the CHARMM36 NA force
field with the CHARMM22 protein force field because there are few
nonbonded changes, but is there any reason you can't use the CHARMM36
protein force field? It can be freely downloaded from the MacKerell web
site, and is supposed to be a drop-in replacement and a significant
improvement over CHARMM22.
- By the way, there does not exist a CHARMM27 protein force field.

> By the way does it possible to make refiriment of my cGMP (with big
> penalties) with VMD plugins and make penalty estimation again?

Nope. Assuming the optimization went well and the resulting charges and
parameters look physical, the only way to get an idea of the quality of
*optimized* parameters is to run experimental validation.

See also the following paper for details on how the penalties are calculated:
K. Vanommeslaeghe, E. P. Raman, A. D. MacKerell Jr., J. Chem. Inf. Model.
2012, 52, 3155-3168.



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