[gmx-users] residue titration w/ FEP

[paloureiro at biof.ufrj.br]

Surlignage "David L. Bostick" <dbostick at physics.unc.edu>:

> 
> 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
> 

The workaround that I have used was:
1)state A = H atom
2)state B = DUM atom
3)DUM atom has C6 and C12 = 0.0, but has some mass (you can put this value in 
your protein.itp file in the [ atoms ] section)
4)the bonded interactions remain the same
5)you will have to add in the [ pairs ] section or directly in the ff*nb.itp a 
null value for the 1-4 interactions with DUM atom.

What dou you think about it?

Regards,

Pedro.