[gmx-users] Umbrella sampling question

[Aswathy]

Hi Chris,
Thank you very much for your reply.

I will give you more details on my US.
Initially ligand is positioned at the starting of the channel and pulled
down wards.(SMD)

1. I have generated all configurations from the SMD(trjconv).
2. Created one index group for center of the channel and another for ligand.
3. Generated a summary_distance file (g_dist) using these index groups
4. Window spacing selected as 0.1nm.
5. run Us with the follo: p[arameters.

pull                     = umbrella
pull_geometry            = position
pull_dim                 =  N N Y
pull_start               = no
pull_nstxout             =  10
pull_nstfout             =  10
pull_ngroups             =  1
pull_group0              =  U_ref(channel center)
pull_pbcatom0            = 0
pull_group1              =  LIG
pull_pbcatom1            = 0
pull_init1               =  0 0 0
pull_k1                  =  1000
pull_rate1               = 0
pull_vec1                =  0 0 0

pull_init 0 0 0 represent the sampling of minimum g_dist value (ligand near
to center of the channel). for positive Z axis, it may change as 0 0 0.1, 0,
0, 0.2 etc. along -z axis, it is 0 0 -0.1, 0, 0, -0.2 etc.
6. initial 400PS  took as equilibration during PMF plot.
http://s980.photobucket.com/albums/ae290/aswathys/?action=view&current=PROFILE-eq400.jpg

If the PMf is not converged, does it means we need to sample more time or
with higher force constant or need to sample more configurations?

Could you please tell me more on the point that you suggested "check the
probability histograms and ensuring that they tend away from the center of
restraint and toward local minima". ?

Thanks in advance.
On Mon, Sep 20, 2010 at 6:22 PM, <chris.neale at utoronto.ca> wrote:

> Aswathy:
>
> We can't tell if you did US correctly unless you post what you have done.
> You must give more info and you must copy and paste the actual input / .mdp
> parameters that you used.
>
> As for if your PMF is correct, then we can never tell you that. You can,
> however, ensure that your sampling distributions are compatible with the PMF
> that you get out of WHAM by looking at the probability histograms and
> ensuring that they tend away from the center of restraint and toward local
> minima on your PMF.
>
> There are hundreds of reasons why your PMF might be wrong (note that it
> also might be correct!) but that is impossible for us to tell with the
> information that you have provided. At the very least, one would need to see
> the PMF and all of the info I mentioned above. Also, you should check (and
> show us!) convergence. If you PMF is still drifting with increasing sampling
> (or increased initial time discarded as equilibration) then you are simply
> not converged for sure.
>
> Chris.
>
> -- original message --
>
> Hi Gromacs users,
> Let me give an idea about what i am doing.
> I was doing a Steered Molecular dynamics of ligand transport through
> the transporter channel. I want to do the PMF calculation using
> Umbrella sampling. I followed the steps provided in the (Justin's)
> tutorial. I have generated all configurations, then used the perl
> script to find out the distance. I made  one index group for 3 back
> bone atoms at the center of the channel and another for the ligand.
> (Therefore I will get the distance between the center of the channel
> and ligand).
> Then I sampled each frame with a window spacing of 0.1nm. The frame
> close to the center of the channel is taken at the 0 th
> coordinate(pull_init=0 0 0). above this point is +Z coordinate and
> below this point is -Z coordinate. I had  good overlapped histograms
> and went ahead with plotting PMF.
>
> Am I doing the correct procedure for Umbrella sampling?
> Why I doubt because,
>  I run g_wham and I had a PMF plot in which at the starting of the
> transport (from extracellular), I have free energy value of
> -35kcal/mol. Then as it moves along the pathway it increases and
> finally it reaches a positive value, +5kcal (when at intracellular).
>
> I know its hard give explanation to my observation, but I am confused
> due to several reasons.
> 1.The energy increases is not much explainable with interactions of
> ligand and transporter.
> 2.If I take the free energy barrier value it is great value than I
> expected. Nearly 170KJ/mol
> 3.In similar kind of ligand transport Smds the PMF was continuous
> maxima and minima.
>
> Can any one tell whether my US procedures were right or not?
>
> Thanks,
>
>
> --
> Aswathy
>
>
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-- 
Aswathy
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