[gmx-users] PMF when pulling in -Z direction

[Justin A. Lemkul]

nahren manuel wrote:
> Hi Justin,
> If you observe my pulling simulation, you will see that the distances 
> are (increasing) in the negative.
> 

Exactly as you expect.  You're pulling along the -Z dimension, as you said 
before.  So the ligand is pulled from the protein to an increasingly negative 
position.

> Here is the PMF (image):
> http://www.flickr.com/photos/nahrenmascarenhas/6312990056/
> this is not one expects in ligand unbinding. (of course these are from 
> my initial simulations, approx. 1 ns runs in 5 windows)
> 

Don't base any conclusions on what you see.  The simulation time and number of 
windows are both woefully insufficient to make any reliable observations.  Only 
once you have done a proper set of umbrella sampling windows will you be able to 
tell what's going on.  You should also be doing error estimates when computing 
the PMF; I suspect the error bars will be as wild as the values in the PMF plot.

-Justin

> Best,
> nahren
> 
> ------------------------------------------------------------------------
> *From:* Justin A. Lemkul <jalemkul at vt.edu>
> *To:* nahren manuel <meetnahren at yahoo.com>; Discussion list for GROMACS 
> users <gmx-users at gromacs.org>
> *Sent:* Friday, November 4, 2011 7:44 PM
> *Subject:* Re: [gmx-users] PMF when pulling in -Z direction
> 
> 
> 
> nahren manuel wrote:
>  > Dear Gromacs Users,
>  >
>  > I am trying to study ligand unbinding adopting Umbrella sampling 
> (using Gmx 4.5.3). during my initial pull to generate configurations for 
> umbrella windows I have pulled in the -Z direction,
>  > @ s0 legend "0 Z"
>  > @ s1 legend "1 dZ"
>  > 0.0000    7.37361    -0.33625
>  > 0.0200    7.37377    -0.33631
>  > 0.0400    7.37404    -0.33637
>  > 0.0600    7.3744    -0.33643
>  > 0.0800    7.37473    -0.33649
>  > .
>  > .
>  > .
>  > .
>  > 321.0800    7.37523    -1.29949
>  > 321.1000    7.37442    -1.29955
>  > 321.1200    7.37374    -1.29961
>  > 321.1400    7.37355    -1.29967
>  > 321.1600    7.37404    -1.29973
>  > 321.1800    7.37491    -1.29979
>  > 321.2000    7.3757    -1.29985
>  > 321.2200    7.37608    -1.29991
>  > 321.2400    7.37595    -1.29997
>  > 321.2600    7.37518    -1.30003
>  > 321.2800    7.37395    -1.30009
>  > .
>  > .
>  > .(so on)
>  >
>  > Now when I ran simulations in each umbrella windows, the PMF energies 
> are in negative.  My guess is that this is due to my initial setup, or 
> is there something seriously wrong. And if i am right I should get the 
> correct PMF by taking the negative of this PMF (or is it)??
> 
> So your PMF is negative, why is that a problem?  A negative binding 
> energy indicates favorability of binding.
> 
> -Justin
> 
>  > -----
>  > ; Pull code  (pulling simulation)
>  > pull            = constraint
>  > pull_geometry  = distance    pull_dim        = N N Y
>  > pull_start      = yes        pull_ngroups    = 1
>  > pull_group0    = Protein
>  > pull_group1    = MAL
>  > pull_rate1      = 0.005          ;
>  > pull_k1        = 1000          ; kJ mol^-1 nm^-2
>  > pull_nstxout    = 500      ; every 1 ps
>  > pull_nstfout    = 500      ; every 1 ps
>  >
>  > -----
>  >
>  > ; Pull code  (Umbrella simulation)
>  > pull            = umbrella
>  > pull_geometry  = distance      ;
>  > pull_dim        = Y Y Y
>  > pull_start      = yes          ;
>  > pull_ngroups    = 1
>  > pull_group0    = Protein
>  > pull_group1    = MAL
>  > pull_rate1      = 0.000          ;
>  > pull_k1        = 1000          ; kJ mol^-1 nm^-2
>  > pull_nstxout    = 500      ; every 1 ps
>  > pull_nstfout    = 500      ; every 1 ps
>  >
>  >
>  > Best,
>  > nahren
>  >
>  >
>  >
>  >
>  >
>  >
> 
> -- ========================================
> 
> Justin A. Lemkul
> Ph.D. Candidate
> ICTAS Doctoral Scholar
> MILES-IGERT Trainee
> Department of Biochemistry
> Virginia Tech
> Blacksburg, VA
> jalemkul[at]vt.edu | (540) 231-9080
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
> 
> ========================================
> 
> 

-- 
========================================

Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

========================================