[gmx-users] PMF of ligand transport
Justin A. Lemkul
jalemkul at vt.edu
Mon May 10 16:51:56 CEST 2010
Aswathy wrote:
>
> Thank you very much for all replies.
>
> No w I just want to try SMd with geometry type as position . But one
> thing is still confusing me, ie; reference group.
>
If you have already generated a suitable set of positions from which you have
generated umbrella sampling windows, you do not need to repeat the SMD. Your
problem was only related to the actual umbrella sampling itself.
> I have the ligand in the solvent (at the mouth of the
> channel(extracellular).) Now I want to pull this ligand to the
> intracellular solvent through the channel. My understanding is that the
> reference group should be the in the same direction of the channel(ie,
> at the intracellular end of the channel), so that if I use "position",
> the ligand should move towards the reference group (Please correct me if
> this wrong). i have only solvent at this end(end of the channel) . Can I
> set water molecules as reference point? or any molecule at this
> intracellular end is fine?
>
In theory, you can set whatever you want, but if those water molecules diffuse,
then you're trying to hit a rapidly-moving target! Always choose a relatively
static part of the structure in the direction you want to pull.
-Justin
> Or else my understanding is wrong?
>
> Please help me
>
> Thank you.
>
> Aswathy
>
>
> On Mon, May 10, 2010 at 6:50 PM, Justin A. Lemkul <jalemkul at vt.edu
> <mailto:jalemkul at vt.edu>> wrote:
>
>
>
> Aswathy wrote:
>
>
>
> On Mon, May 10, 2010 at 6:29 PM, Justin A. Lemkul
> <jalemkul at vt.edu <mailto:jalemkul at vt.edu>
> <mailto: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>>
> <mailto: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>>>
> <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
> <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>>>>
> <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
> <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>>>
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> <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>>>
> <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>
> <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> <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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