[gmx-users] PMF of ligand transport
Justin A. Lemkul
jalemkul at vt.edu
Mon May 10 14:59:44 CEST 2010
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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