[gmx-users] PMF of ligand transport

Aswathy ammasachu at gmail.com
Mon May 10 13:50:12 CEST 2010


I am pulling through the channel with respect to a single residue on one
"side"(extracellular) of the structure. I have used pull_geometry = distance
&  pull_dim =  N N Y. From this what I understood is ligand will pull along
the z direction with respect to the reference group (away from r_57).  (i.e
from extracellular to intracellular). Is this correct?

Here is my umbrella sampling .mdp parameters

pull                     = umbrella
pull_geometry            = distance
pull_dim                 =  N N Y
pull_start               = yes
pull_nstxout             =  10
pull_nstfout             =  10
pull_ngroups             =  1
pull_group0              =  r_57
pull_group1              =  r_C1
pull_k1                  =  1000
pull_init1               =  0

On Mon, May 10, 2010 at 4:50 PM, Justin A. Lemkul <jalemkul at vt.edu> wrote:

>
>
> Aswathy wrote:
>
>> Thanks for your  reply.
>>
>>  In this case reference (r57) is not the part of the channel. But it is a
>> residue in the loop above the channel entry. Thats why I used
>> pull_geometry=distance. Therefore I am pulling the ligand away from this
>> reference.
>>
>>
> So you are not pulling through the channel?  Or you are pulling through the
> channel with respect to a single residue on one "side" of the structure?  If
> your ligand ever crosses over this reference in any way, the reference
> distance will change sign and thus Tom is right, you should use
> "pull_geometry = position."  With "distance," you can only ever have
> positive reference distances.
>
> What are your .mdp settings during umbrella sampling?
>
> -Justin
>
>  Thanks
>> -Aswathy
>>
>>
>> On Mon, May 10, 2010 at 3:05 PM, Thomas Piggot <t.piggot at soton.ac.uk<mailto:
>> t.piggot at soton.ac.uk>> wrote:
>>
>>    Hi,
>>
>>    If you defined the reference (r_57) as part of your channel then
>>    with pull_geometry=distance you will have problems as the distance
>>    between pull_group1 and pull_group0 becomes closer to zero and then
>>    the distance becomes positive again.
>>
>>    I recently had this with my umbrella sampling simulations. Search
>>    for the discussion of things you can do to address this issue on the
>>    list. To stop this being a problem in the first place you should
>>    have used pull_geometry=position.
>>
>>    Cheers
>>
>>    Tom
>>
>>    Aswathy wrote:
>>
>>        Can any one help me please? I looking forward to hear from any
>>        of you.
>>        Thank you.
>>
>>
>>        On Thu, May 6, 2010 at 1:19 PM, Aswathy <ammasachu at gmail.com
>>        <mailto:ammasachu at gmail.com> <mailto:ammasachu at gmail.com
>>
>>        <mailto:ammasachu at gmail.com>>> wrote:
>>
>>           Ok i will explain you in detail.
>>
>>            Initially i pulled the ligand through the protein channel ,
>>        using
>>           the given parameters.
>>
>>           pull                     = umbrella
>>           pull_geometry            = distance
>>           pull_dim                 =  N N Y
>>           pull_start               = yes
>>           pull_nstxout             =  10
>>           pull_nstfout             =  10
>>           pull_ngroups             =  1
>>           pull_group0              =  r_57
>>           pull_group1              =  r_C1
>>           pull_rate1               =  0.01
>>           pull_k1                  =  1500
>>
>>           Then I extracted the frames from the trajectory using the perl
>>           program provided with tutorial. COM distance I took as nearly
>>        0.12
>>           nm. (But sometimes I failed to obtain frames exactly at that
>>           interval, but took  nearly at 0.12). Each frame I used for
>>        Umbrella
>>           sampling for 1ns.
>>           Then I checked histograms for overlapping (Some histograms were
>>           entirely overlapped and I removed that from the list, where ever
>>           gaps i selected new frames and did sampling so that I can get an
>>           evenly distributed histograms , I know this will change the
>>        overall
>>           COM distribution but is there any other way to solve this?) .
>>
>>           Finally once I obtained reasonably good overlapped histograms, I
>>           plotted PMF using g_wham. The plot  was a steeply increasing
>>           potential.  How can we get increased PMF even when the ligand is
>>           reached out of the channel?
>>
>>
>>                    Did I made any mistake any where , I am confused.
>>
>>           Thank you.
>>           -Aswathy
>>
>>
>>
>>           On Thu, May 6, 2010 at 12:56 PM, Jochen Hub
>>        <jochen at xray.bmc.uu.se <mailto:jochen at xray.bmc.uu.se>
>>           <mailto:jochen at xray.bmc.uu.se
>>        <mailto:jochen at xray.bmc.uu.se>>> wrote:
>>
>>               Aswathy wrote:
>>
>>
>>                   Hi gromacs users,
>>
>>                   I am using Gromacs 4.0.4 package. I am doing SMD of a
>>        ligand
>>                   transport through a channel.
>>
>>                   I performed SMD and did umbrella sampling (Thanks to
>>        Justin
>>                   for his  tutorial). Extracted frames with a window
>>        spacing
>>                   interval  of ~0.12nm. and did 1ns sampling.
>>        Histograms are
>>                   with reasonabvle overlap. Then I used g_wham for
>> plotting
>>                   PMF considering first 300ps as equilibration.
>>
>>               Isn't SMD usually referred to pulling at some finite pulling
>>               speed? That would not be umbrella sampling.
>>
>>               Anyway, you'll have to provide a lot more data to enable
>>        us to
>>               help you.
>>
>>               Jochen
>>
>>
>>
>>
>>                   I am getting a plot , but potential is increasing
>>                   constantly. ie, PMF is not converged as mentioned the
>>                   tutorial? Do I need to extend the sampling ? or any
>> other
>>                   reason?
>>
>>                   Please help me.
>>                   Thank you.
>>
>>                   -Aswathy
>>
>>
>>
>>               --
>>  ---------------------------------------------------
>>               Dr. Jochen Hub
>>               Molecular Biophysics group
>>               Dept. of Cell & Molecular Biology
>>               Uppsala University. Box 596, 75124 Uppsala, Sweden.
>>               Phone: +46-18-4714451 Fax: +46-18-511755
>>               ---------------------------------------------------
>>
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>>
>>
>>
>>           --     Aswathy
>>
>>
>>
>>
>>        --         Aswathy
>>
>>
>>    --     Dr Thomas Piggot
>>    University of Southampton, UK.
>>
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>>
>>
>>
>> --
>> Aswathy
>>
>>
> --
> ========================================
>
> Justin A. Lemkul
> Ph.D. Candidate
> ICTAS Doctoral Scholar
> MILES-IGERT Trainee
> Department of Biochemistry
> Virginia Tech
> Blacksburg, VA
> jalemkul[at]vt.edu | (540) 231-9080
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>
> ========================================
>
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-- 
Aswathy
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