[gmx-users] Weird result of WHAM

[Netaly Khazanov]

You are right, I am not expecting to get exactly the same PMF for
trajectory A -->B and B -->A.
But I do expect to get at least the same trend for the end states of the
trajectory.

On Thu, Nov 15, 2012 at 10:22 AM, Jianguo Li <ljggmx at yahoo.com.sg> wrote:

> If the two end states of a system are fixed, the free energy difference is
> independent of the path. I am not sure what caused the problem, but if
> besides the protein, water and ions, there are some other molecules in your
> simulation box (e.g., membrane or ligand), the states A and B of your
> protein from trajectory A->B may not be exactly the same as those from the
> trajectory B->A. In such a case, it is not strange to have different PMFs.
>
>
> --Jianguo
>
>
>
> ----- Original Message -----
> From: Netaly Khazanov <netalyk at gmail.com>
> To: Discussion list for GROMACS users <gmx-users at gromacs.org>
> Cc:
> Sent: Thursday, 15 November 2012, 15:41
> Subject: Re: [gmx-users] Weird result of WHAM
>
> Sorry, I will express  myself more clearly.
> 1.State A/B  corresponds  to  different conformation states of the protein.
> State A is the crystal structure of the protein, suppose to be more stable
> than state B (model structure).
> And indeed, I've got the expected PMF plot in which clearly can be seen,
> that state A is more stable than state B by taking snapshots  from the path
> A to B.
> In order to check myself, I did the same to the snapshots that were taken
> from the trajectory path from the B to A and I've got the opposite results.
> ( State B is more stable than state A by the same magnitude of delta G!)
>
> Umbrella sampling for 10ns :
> ; Pull code
> pull            = umbrella
> pull_geometry   = distance
> pull_dim        = Y  Y  Y
> pull_start      = yes
> pull_ngroups    = 1
> pull_group0     = O1G_O2G_O3G_PG_&_ATP
> pull_group1     = r_90
> pull_init1      = 0
> pull_rate1      = 0.0
> pull_k1         = 1000      ; kJ mol^-1 nm^-2
> pull_nstxout    = 1000      ; every 2 ps
> pull_nstfout    = 1000      ; every 2 ps
>
> Wham analysis command:
> g_wham_d -it tpr-files.dat -if pullf-files.dat -o -hist -unit kCal -b 1000
>
> 2. By merging  the data of the both path, I meant that I added tpr files
> and pullf files from the path B to A  to the
> files tpr-files.dat/ pullf-files.dat of the path A to B and calculated
> WHAM.. I can do it since it is the same reaction coordinates in both cases,
> can't I?
> The result PMF plot shows that state A is more stable than state B like I
> expected.
> So I really don't know what I am doing wrong while analysing
> the snapshots from path B to A.
> Any ideas?
> Thanks
>
>
>
> On Wed, Nov 14, 2012 at 8:40 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
> >
> >
> > On 11/14/12 8:43 AM, Netaly Khazanov wrote:
> >
> >> Dear All,
> >>
> >> I've performed TMD simulation using NAMD program from the state A to B,
> >> and
> >> visa versa from the state B to A.
> >> Umbrella sampling calculations were done on the snapshots that were
> taken
> >> from the path ( A to B & B to A) by using Gromacs.
> >> Afterwards WHAM analysis was calculated in order to extract PMF plot.
> >> However the result of  ΔG of PMF plot  in the case of A to B path was
> the
> >> opposite (for example -10)  than in the case of B to A ( 10). ( I would
> >> expect to get the same result in both cases).
> >>
> >
> > Can you explain in greater detail what states A and B correspond to?  I
> > would expect the opposite - the reverse of a process should have the same
> > magnitude of deltaG and opposite sign (i.e. ligand binding/unbinding).
> >
> >
> >  By merging the data of both paths, WHAM gives result of   ΔG=-10.
> >> The result is very not consistence. I'm  probably missing something.
> >>
> >
> > You'll have to be more explicit about what you're doing, i.e. actual
> > commands, input, and output.
> >
> > -Justin
> >
> > --
> > ==============================**==========
> >
> > Justin A. Lemkul, Ph.D.
> > Research Scientist
> > Department of Biochemistry
> > Virginia Tech
> > Blacksburg, VA
> > jalemkul[at]vt.edu | (540) 231-9080
> > http://www.bevanlab.biochem.**vt.edu/Pages/Personal/justin<
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin>
> >
> > ==============================**==========
> > --
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> --
> Netaly
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-- 
Netaly