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

[François-Régis Chalaoux]

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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