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

[François-Régis Chalaoux]

Thanks Alex, finding the positions as you propose seems a legitimate way
for this problem. One will have to wait enough with a classical MD but Bias
MD should help. In my case the channel is not a large ion channel.

FR.

2017-06-22 18:26 GMT+02:00 Alex <nedomacho at gmail.com>:

> 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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