[gmx-users] Negative arginine?

[Steven Spronk]

On Tue, 30 Nov 2004, Anton Feenstra wrote:

> IMHO, it is not reasonable at all. You'd want a 'physical system' that
> could at least in principle correspond to a real state, which in your
> proposed case you clearly have not. What kind of 'control' simulations for
> your WT (as per your previous mail) did you have in mind?
>
> --
> Groetjes,
>
> Anton

Thank you David, Anton, and Erik for your comments so far.  It sounds like
it's difficult to justify arbitrarily messing with charges.  I'm glad that
I'm getting this feedback before I'm very far into the simulations.

Let me explain a little more why we're thinking about these charge
manipulations.  The particular arginine I'm talking about is on a
transmembrane helix of a voltage sensitive protein, and is exposed to
lipid, not solvent.  Obviously this is an unusual arginine.  We're
exploring the idea that the arginine contributes to the voltage
sensitivity of the protein by moving vertically through the bilayer in
response to an electric field.  The interaction with the applied field, of
course, depends only on the charges on the atoms.  Hence, I thought that
it would be interesting to see how things behaved differently if I changed
the charges on the atoms while not changing all the interactions with the
lipids.  We're trying to manipulate the arginine's ability to sense the
field while not perturbing the rest of the interactions too much.  I do
realize, however, that the charges of the side chain interact with all the
charges around (although the lipid atoms are all uncharged, there are
other side chains and backbone atoms around).

But basically, we have a simulation of the protein in an electric field,
and now we want a similar simulation in which we keep the same field on
the system but force the arginine to move against the field, not with it.
Do any of you think that such a manipulation has any real advantage over,
say, mutating the arginine to a glutamate?

Thank you!
Steve