[gmx-users] PMF of ligand transport
Justin A. Lemkul
jalemkul at vt.edu
Mon May 10 15:20:54 CEST 2010
Aswathy wrote:
>
>
> On Mon, May 10, 2010 at 6:29 PM, Justin A. Lemkul <jalemkul at vt.edu
> <mailto: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)?
>
A residue with a more predictable position is probably preferable. If the loop
moves a lot (or even somewhat), the umbrella potential will attempt to maintain
the specified reference distance, so you could get spurious forces.
-Justin
> 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>
> <mailto: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>>
> <mailto: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>>>
> <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
> <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>>>
> <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
> <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> <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 <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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