[gmx-users] PMF of ligand transport
Aswathy
ammasachu at gmail.com
Mon May 10 15:18:57 CEST 2010
On Mon, May 10, 2010 at 6:29 PM, Justin A. Lemkul <jalemkul at vt.edu> wrote:
> Ok . Now I understood. I have one more doubt , as I mentioned to you, I am
> using one residue in the extracellular loop as a reference point. Since this
> is in the loop, do you think it can be good reference point (due to th large
> fluctuatuion in the loop, will it affect the result)?
>
> Aswathy wrote:
>
>> 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?
>>
>>
> I don't think so. If you are pulling through a channel, using an
> extracellular residue as a reference, you will be changing the sign of the
> distance, rendering "pull_geometry = distance" useless. For example, in
> order to properly calculate the PMF, you have to pull from the aqueous
> solvent, into the channel, then back out into the solvent. At some point,
> your ligand is outside the channel (such that, for example, the z-coordinate
> of the ligand is greater than that of r_57, so distance > 0). Then, as your
> ligand enters the channel, its z-coordinate is less than that of r_57, so
> distance < 0. If this is the case, you must use "pull_geometry = position"
> to get the correct signs, otherwise your umbrella sampling window reference
> distances will be nonsensical.
>
> -Justin
>
> 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<mailto:
>> 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>
>> <mailto: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>>
>> <mailto: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>>
>> <mailto: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 <http://vt.edu> | (540) 231-9080
>>
>> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>>
>> ========================================
>>
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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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