[gmx-users] Pulling inside a channel to calculate the PMF

[Alex]

I've never used PLUMED, to be honest, so I don't know.

If ligands are salt ions or any other overall charged entities, I would 
solvate the channel (with restraint, maybe) for essentially a production 
run and apply an electric field "parallel" to the channel lumen, then 
just visualize the trajectory and pick the configurations by hand. gmx 
trjconv can -dump any particular frame of your liking. Maybe not as 
automated as one could hope, but then you will know in-depth what 
configs you have.

Alex

On 6/22/2017 3:03 AM, François-Régis Chalaoux wrote:
> Hi Alex,
>
> There is no confusion about the pulling that is only a preparation for
> WHAM, but as you tell it you need to choose positions. These positions
> could be choosen manually: if one choose to explore the static channel from
> apo, then I'm agree, select the positions in the channel "in a bunch of
> reasonably spaced spots along the curved "axis" of your channel, each
> followed by equilibration and the production run, yielding the data useful
> for WHAM". As you say, you need time and patience. Could PLUMED (or
> somethoing else) /Gromacs be used to automate this ?
>
> On the other side, this channel come from a static APO structure and the
> reality of this channel is tiedous, so why not discover dynamically the
> channel and run the next equilibration and the production run on the fly, could
> PLUMED (or somethoing else)/Gromacs  be used to automate this ? How to
> discover the channel on the fly ? May be it is feasible to use simply the
> coordinates of the channel discovered by MDPocket with a long classical MD
> realized  previously on the apo/holo structure ?
>
> FR.
>
> 2017-06-22 10:19 GMT+02:00 Alex <nedomacho at gmail.com>:
>
>> I think your problem is solvable with enough perseverance, but there may
>> also be some confusion... The PMF calculation isn't based on the data
>> obtained from an actual pull: the pulling rate in those simulations is set
>> to zero. The reason for using pull code there is to pull (pun intended) the
>> positions and/or forces. The initial structures, of course, is where e.g.
>> Justin's tutorial uses pull along a straight line.
>>
>> However, if you have the time and patience, you could of course
>> (manually?) put your ligand in a bunch of reasonably spaced spots along the
>> curved "axis" of your channel, each followed by equilibration and the
>> production run, yielding the data useful for WHAM.
>>
>> Hope this helps.
>>
>> Alex
>>
>>
>> On 6/22/2017 2:05 AM, François-Régis Chalaoux wrote:
>>
>>> Hi everybody,
>>>
>>> I would like to pull a ligand in a channel from my protein and calculate
>>> the PMF with Umbrella sampling. This channel is probably not linear and
>>> thus have to be defined. Too much colisions appears along a simple one
>>> axis
>>> pulling and causing a catastrophic PMF calculation.
>>>
>>> Currently I'm working with Gromacs and I wondered if it is possible to
>>> define statically or dynamically the coordinates for the center of the
>>> channel and use it during the simulation (Pulling).
>>>
>>> One solution could be to define in the md_pull.mdp configuration file all
>>> the transition points of my pathway through which my ligand must pass from
>>> my APO structure determined with CAVER.
>>> Instantiation of Gromacs parameters of md_pull.mdp is not enough clear for
>>> me and PLUMED is may be a more direct solution. Currently I have no
>>> experience with PLUMED but It seems on paper to be able.
>>>
>>> An other choice would be to define dynamically the channel center,
>>> on-the-fly. PLUMED seems also capable to manage this sort of challenge but
>>> once again I have no idea of the feasibility of a such work.
>>>
>>>
>>> What do you think about this problem and of the tracks evoked above ?
>>>
>>>
>>> Cheers, FR.
>>>
>>> *Pulling inside a channel to calculate the PMF*. Available from:
>>> https://www.researchgate.net/post/Pulling_inside_a_channel_t
>>> o_calculate_the_PMF#594b792648954cf7f2759a48
>>> [accessed Jun 22, 2017].
>>>
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