Why am I getting constant lambda values in constant pH MD for a tripeptide system?

User discussions
1

GROMACS version:
GROMACS modification: Yes/No
Hi,
I am using constant pH GROMACS to simulate two gly-asp-gly tripeptides. I am using the phbuilder tool to generate the necessary input files to run constant pH MD, and following the instructions given in the pHbuilder gitlab page. I am trying to generate the titration curve given in this paper- https://pubs.acs.org/doi/10.1021/acs.jctc.2c00516. But when I plot the change of lambda with time, I don’t observe any fluctuation of it. I see the lambda values are constant. If the ph is 3 (which is less than the pka value of Asp), the lambdas are constant at 0. And if the ph is 4, the lambdas are constant at 1. Why is it like that? I simulated this system changing a few parameters like number of buffer particles, but nothing worked. It would be highly helpful if I get an answer of why the lambda values are constant. What could be possible reasons?

Thanking you,
Sanjib

2

Hi Sanjib,

Your observation makes sense to me. A lambda value of 0 means that the ASP side chain is protonated at pH 3, while a lambda value of 1 at pH 4 indicates the deprotonated form. However, I would expect some fluctuations during your simulations, because pH 3 and pH 4 are relatively close to the parameterised pKₐ value. What does your .mdp file look like? Did you set lambda-dynamics-calibration = no?

Best,
Marius

3

Hi Marius,

Thank you for your response. I also expect fluctuations in the lambda values. I have set
lambda-dynamics-calibration = yes.
md_prod.mdp (4.0 KB)
I have attached the .mdp file here. Please have a look.

Thanking you,
Sanjib

4

There it is! If you set lambda-dynamics-calibration=yes GROMACS will keep your lambda value fixed during the simulation. Please take a look at the documentation: manual/constantph_usage.md · main · Gromacs constant ph / Constantph · GitLab

Best,
Marius

5

Thank you so much, Marius!