[gmx-users] Weird result of WHAM

[Jianguo Li]

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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