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, FabrÃcio Bracht <fabracht1.gmail.com>
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
> FabrÃcio
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>
--
Jason M. Swails
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Received on Wed Dec 14 2016 - 20:30:03 PST
