From: Axel Kohlmeyer (
Date: Mon Oct 26 2009 - 10:42:13 CDT

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?

> 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.


> 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.


> Cheers,
> Michel


Dr. Axel Kohlmeyer 
Institute for Computational Molecular Science
College of Science and Technology
Temple University, Philadelphia PA, USA.