Dear Jason and Francois,
Many thanks for your replies.
Francois, I was thinking of taking charges from GLH in amino12.in, and
adjusting the charges in line with the changes between GLU in amino12.inand
aminoct12.in. In this way, the issues you mention regarding differences
between carboxylic acid and carboxylate don't apply for the side-chain. I
already noticed that changes in GLU charges in amino12.in and
aminoct12.inare quite small, and therefore thought that
'extrapolating' these changes
for a C-terminal GLH might be OK.
Jason, I want to run standard MD at a pH around 4 (not uncommon in NMR
experiments, for example). Under those conditions, one would expect a
(solvent exposed) Glu side-chain to be (partly) protonated (pKa ~4.25)
whereas a C-terminal carboxylate may well be unprotonated (pKa ~3.67, see
e.g. Thurkill et al., doi: 10.1110/ps.051840806).
So, I didn't think that a C-terminal GLH is so strange, at least not within
the limitations of standard MM MD.
But perhaps there is a good reason that C-terminal GLH is never present in
standard AMBER forcefields?
Would people find it strange (e.g. as a reviewer) to see a simulation with
a C-terminal GLH?
Thanks,
Marc
On 3 June 2012 07:18, FyD <fyd.q4md-forcefieldtools.org> wrote:
> Dear Jason and Marc,
>
> >> 2) If not, would a 'simple' solution, in which I'd just add the atoms in
> >> analogy to GLU and then manually change the charges similarly to the
> >> changes between GLU in amino12.in and aminoct12.in, be OK? Or would
> >> redeveloping the charges (e.g. with RED) be the only appropriate
> solution?
> >
> > My approach (and others may disagree here) is that if the changes you
> would
> > make by hand are fairly small, there's probably not much need to
> re-derive
> > charges. If the charge differences are large, then rederiving may be an
> > appropriate option, although you'll have to take care to apply
> > 'appropriate' charge constraints for consistency. (hopefully
> hand-editing
> > will work).
>
> I would re-compute the charge values for three main reasons:
> - the differences in charge values for a molecule can be important
> when one compares an anion/carboxylate and a neutral molecule/carb.
> acid.
> - the optimized geometry for an anion and a neutral molecule are
> generally different
> - finally the charge derivation procedure itself can be different;
> i.e. for neutral terminal fragment one might not adopt an approach
> involving 2 building blocks.
>
> regards, Francois
>
>
>
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Received on Tue Jun 05 2012 - 09:00:03 PDT
