[gmx-users] PMF for Carbohydrate-Protein

[Sai Kumar Ramadugu]

Dear All,
I'm running set of umbrella sampling simulations to get the PMF of a
disaccharide binding to a protein.
I followed the tutorial provided by Justin and changed the values of
necessary parameters according to my system.
The mdp file for umbrella sampling simulations is as follows:
-------------------------------------------
; Pull code
pull                    = umbrella
pull_geometry   = distance      ; can't get PMF with direction
pull_dim            = N N Y
pull_start           = yes
pull_ngroups    = 1
pull_group0       = active_site
pull_pbcatom0   = 575
pull_group1       = new
pull_pbcatom1   = 1500
pull_init1             = 0
pull_rate1           = 0.0
pull_k1               = 750           ; kJ mol^-1 nm^-2
pull_nstxout        = 1000          ; every 2 ps
pull_nstfout         = 1000          ; every 2 ps
----------------------------------------------------

Active site in the pull_group0 being the residues in the binding site and
new in the pull_group1 being the disaccharide.
Initially I did an SMD run where I separated the disaccharide from the
binding upto 1.5nm in distance.

When I started running the umbrella sampling simulations, I used the
conformations with approximately 0.1nm difference starting from an
initial separation of 0.3nm between the binding site residues and
disaccharide.
My question is: when I run g_wham and get the profile, the pmf reaches a
plateau, but its not completely horizontal. It drops down a little. Is it
acceptable to have the pmf reach a plateau but not completely horizontal?
In the histogram, the first two windows have good overlap and are narrow
distributions where as the later windows are spread out.
I have tried to decrease the distance from 0.1 nm to 0.05 nm and still the
sampling around 0.5-0.75 of Xi region does not sample well.
Is there anything that you could suggest?

I have uploaded the plots of profile and histograms.

PMF Plot link: http://img801.imageshack.us/i/pmf.png/
Histogram link: http://img217.imageshack.us/i/histoy.png/


Thanks for your time

Sai Ramadugu
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