VMD-L Mailing List

From: L. Michel Espinoza-Fonseca (mef_at_ddt.biochem.umn.edu)
Date: Mon Oct 26 2009 - 10:54:56 CDT

On Mon, Oct 26, 2009 at 4:42 PM, Axel Kohlmeyer <akohlmey_at_gmail.com> wrote:

> On Mon, 2009-10-26 at 16:24 +0100, L. Michel Espinoza-Fonseca wrote:
>
> > I have performed long simulations of peptides using SPC and SPC/E
> > water models and in general I observed that it increases the helical
> > content (compared to experiments). In some cases with peptides that
>
> ...and compared to TIP3P?
>
>
Very good point that I missed to mention. TIP3P was better in reproducing
NMR/CD data compared to SPC and SPC/E. In some cases when the peptide is
natively unstructured, you could even see how it rapidly (i.e., after a few
nanoseconds) shifts to a random coil.

> > are supposed to be unstructured in solution, you can observe a large
> > amount of helical content that does not match the experimental results
> > (even considering that a peptide does not exist as a fully random coil
> > under highly denaturant conditions). I personally don't have anything
> > against on in favor when it comes to particular water models, but I'm
> > just trying to stress on the fact that it is not recommendable to mix
> > different force fields, either for technical reasons or because of the
> > physical meaning of the trajectories you get.
>
> for the most part, i agree with you here. hence my warning in the
> original response. there are a few cases, where there may be some
> value in doing it anyways, but - as you pointed out - one cannot
> rely on the modeling of the protein structure being consistent
> with its parametrization.
>
> [...]
>

I'm glad we agree on this :-)

>
> > Even though a convincing proof is always the best option, I'm using my
> > previous experience with this water model, the CHARMM force field and
> > a bit of intuition to propose a situation that could likely happen if
> > you combine both force fields. A larger competition between
> > backbone-backbone and water-backbone hydrogen bonds might be
> > compensated by the CMAP correction (if used, of course), so it is
> > still possible that at the end your protein remains too helical.
>
> agreed. in the end it doesn't even matter so much whether it would
> be too helical or not helical enough. it is simply inconsistent to
> mix and match components of different force fields, especially as
> vital ones as the water potential.
>

> thanks for the discussion and sharing your experiences.
> i think this is very helpful to people that get tempted
> to "improve" their water by using a different potential
> for it.
>
>
No problem :-). It is always very nice to have a very good brainstorming,
which at the end makes you feel even more curious and aware about the
advantages/limitations of the existing models.

Cheers,
Michel

> cheers,
> axel.
>
> > Cheers,
> > Michel
> >
>
> >
> --
> Dr. Axel Kohlmeyer akohlmey_at_gmail.com
> Institute for Computational Molecular Science
> College of Science and Technology
> Temple University, Philadelphia PA, USA.
>
>