Re: [AMBER] Constant pH across membrane

From: Fabrício Bracht <>
Date: Thu, 15 Dec 2016 10:58:06 -0200

Hi Jason. When you say treat the lipids themselves as solvent, do you mean
to include them as titratable residues? I didn't quite get what you meant.
Is the Stern's paper you are referring to this one?
I don't have access to the full paper, but thanks anyway for the reference.
We don't have a charmm's license also.
Guess I'll have to see how the results come out.
Thank you

2016-12-15 2:22 GMT-02:00 Jason Swails <>:

> This is a very challenging problem, and probably not one that the explicit
> solvent method in Amber is well-equipped to handle.
> However, as long as you don't treat the lipids themselves as solvent (i.e.,
> they are included in the protonation state change attempts), it's
> *possible* that the results might be reasonable.
> However, purely explicit solvent models will almost certainly be better
> here (e.g., the approach inside CHARMM or Stern et al.'s method for
> discrete protonation states).
> HTH,
> Jason
> On Wed, Dec 14, 2016 at 6:49 PM, Fabrício Bracht <>
> wrote:
> > Hi. I am calculating the PMFs of molecules going across a POPC membrane
> > using umbrella sampling. Up until now, we've worked only with molecules
> > with no titratable groups. But there are some molecules that do have
> > titratable groups (carboxylates and amines mainly). Being so, I thought
> > that I could use CpHMD to get the correct protonation state while going
> > across the membrane. But then I realized that there are some problems
> > related to that. I would like to hear your comments on them.
> > First: If I do parameterize the charges and the free energy in order to
> > reproduce the pKa in water (explicit), although I may have a correct
> > protonation distribution when the molecules are still outside the lipid
> > bilayer (i.e. still in water) I will probably won't have that once they
> are
> > inside the bi layer mainly due to the fact that the actual exchange of
> > protonation states is still done using the dielectric constant of water
> > using implicit solvent.
> > Second: Since pH is valid only in water. It would make sense to sample
> > different protonation states once inside the membrane. So, if I were to
> > sample the protonation states, It would make more sense to do while still
> > in water and maybe in the region near the polar PC groups.
> > Actually, I had more questions on the matter, but I thought about maybe
> > starting with these two and see how you guys respond.
> > If possible, I would very much appreciate some suggestions on the matter.
> >
> > Thank you in advance
> > Fabrício
> > _______________________________________________
> > AMBER mailing list
> >
> >
> >
> --
> Jason M. Swails
> _______________________________________________
> AMBER mailing list
AMBER mailing list
Received on Thu Dec 15 2016 - 05:00:02 PST
Custom Search