How can I get smooth PMF from umbrella sampling

GROMACS version: 2018
GROMACS modification: No

Dear GMX users,

I performed two umbrella sampling simulations of interaction of two short peptides for 20 ns each window. I got some weird PMF figures as I attached. It means that there are sharp curves for both simulations. How can I get smooth PMF?

Second, the converged values of these PMF is around -3 kcal/mol. How reliable are these curves?

Best regards,
Batsaikhan

Look at the histograms. You probably have a few regions of poor sampling/poor overlap.

Dear prof. Justin,
Thank you very much for your prompt reply. I attached one of the histograms. It looks much overlapped. Should I increase simulation time of the windows.

Best regards,
Batsaikhan

You have way too many windows that are almost redundant. There is really uneven spacing across the reaction coordinate. You need to refine your window spacing, force constants, or both. And you may still need more sampling time after you do that.

Dear prof. Justin,

Thank you very much for your clear explanation.

Best regards,
Batsaikhan

Dear prof. Justin,

Hello, thank you for your time.
I performed umbrella sampling simulations for dimer structure of a short peptide.
When I perform WHAM analysis, the histogram is good enough as following. However, the PMF plot is weird. How can I get good PMF curve? Please advice me.


Best regards,
Batsaikhan

Looks fine to me. What do you think is the problem?

Dear prof. Justin,

Thank you very much for your reply. I have tried many times to get this kind of histograms using different forces and different simulation times. Some of calculations showed the higher converging values in profile plot around 1 or 2 kcal/mol. However I used very strong pulling force, I observed uneven distributions in strong pulling simulations.

Therefore, I expected that the profile curve should be converged around positive E values.

Thank you very much again.

Best regards,

Batsaikhan