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
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Received on Wed Dec 14 2016 - 16:00:02 PST
