[gmx-users] residue titration w/ FEP

David L. Bostick dbostick at physics.unc.edu
Tue Aug 23 01:16:10 CEST 2005

Thank you for the help.  There is one thing that I don't understand.  If I
mutate the proton on GLUH to a dummy particle, I imagine that I must write
the dummy constraint into the topology file using the

[ dummies3 ]

tag for the 3fad type of dummy constraint. However, this interaction has no
lambda dependence. This would imply one of 2 things.  Either the angle and
bond for the GLU-H proton would be perturbed away from lambda=0-->1, and at
lambda=1 the dummy constraints would take over, or the dummy constraints
would hold for the entire simulation, making the angle and bond terms for
this proton superfluous parameters. I have no idea which of these gmx does
(if either).

This makes me think that the only (or best) way to perturb away the
interaction would be to treat the proton as a dummy atom for state A as
well as state B ... changing only the nonbonded interactions. I would
really like to know what happens however.  Would anyone who knows about
this please instruct me? Does it really make sense to perturb bond and
angle terms if there is a dummy constraint applied?  If it doesn't make
sense, then wouldn't it be best to just use a dummy atom for the entire
perturbation rather than perturb a real site into a dummy site?

Thanks in advance,

David Bostick					Office: 262 Venable Hall
Dept. of Physics and Astronomy			Phone:  (919)962-0165
Program in Molecular and Cellular Biophysics
UNC-Chapel Hill
CB #3255 Phillips Hall				dbostick at physics.unc.edu
Chapel Hill, NC 27599	           		http://www.unc.edu/~dbostick

On Mon, 22 Aug 2005 paloureiro at biof.ufrj.br wrote:

> >
> > Hello,
> >
> > I am calculating the free energy for deprotonating GLU-H --> GLU.   This is
> > an annihilation FEP exercise. State A is a regular GLUH residue, and State
> > B is the same residue with all bonded interactions the same, but all
> > non-bonded interactios turned off.  Also in state B, the mass of the proton
> > is zero.
> >
> > I run into a problem at the very last window simulation at lambda=1 where
> > the proton has no mass.  Basically the proton moves around wildly w.r.t.
> > the residue and I get LINCS errors that cause the program to crash. I
> > imagine this is because there are no forces on the proton to keep it
> > tethered to the residue.
> >
> > I imagine the solution is to mutate the proton to a dummy atom, but I'm not
> > sure how to do this. Could someone offer help / suggestions?
> >
> >
> Yes, use atom "MW" or "DUM" as state B of the proton and use soft core
> parameters...
> (for instance, sc-alpha=1.5 and sc-sigma=0.3)
> Maybe you will have to use a smaller time step, though.
> Regards.
> Pedro.
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