Inquiry regarding protonation status

User discussions
1

GROMACS version: 2021.6
GROMACS modification: No
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Hello. I am a beginner at simulation and have some questions about the protonation status.

According to what I learned, the way to determine them is:
predict the pKa of residues using some online tools
(for HIS, visualize the output in software like VMD, etc.)
compare the system pH and pKa and determine the protonation status.

Since I did not find descriptions of the protonation status in the tutorials
(GROMACS Tutorials 1 and 5),
I am a little bit confused.

  1. Will the pKa of residues change during the simulation?
    If so, is it still meaningful to specify the protonation status?

  2. A more general question.
    How should we determine the pH for the simulation?
    Is 7.0 applicable for all protein systems (or protein-protein complex without non-protein molecules)?

Thanks in advance.

2

Will the pKa of residues change during the simulation?
If so, is it still meaningful to specify the protonation status?

The “felt” pKa of your residues might change if they undergo considerable environmental changes during the simulation, but residues can’t just (de)protonate on-the-fly (unless you’re running QM/MM on those residues), you need to specify their protonation state prior to the simulation.

A more general question.
How should we determine the pH for the simulation?
Is 7.0 applicable for all protein systems (or protein-protein complex without non-protein molecules)?

That depends on the conditions you want to simulate. You should ask yourself if you’re interested in studying the in vitro or in vivo properties of the protein. If in vitro, your experimentalist should be able to tell you what pH their buffer solution is. If in vivo, what organism? What does the literature say about the pH in the tissue your protein is expressed?

3

Thank you for your reply.
I will search for the information needed.