[gmx-users] Non-symmetric PMF across lipid bilayer

[Gmx QA]

Thanks again

But thinking about this a bit further - if, as you say, wham sets the
leftmost window to zero and calculates energies for all consecutive windows
relative to that, then shouldn't windows that are equivalent in terms of
the molecules being surrounded only by water, but on opposing sides of the
bilayer, have the same relative energy in the PMFs without any cyclization?
I might be missing the finer details about the wham equations here, but
would appreciate some further insights :-)



Den ons 21 nov. 2018 kl 15:49 skrev Justin Lemkul <jalemkul at vt.edu>:

>
>
> On 11/21/18 9:03 AM, Gmx QA wrote:
> > Hi Sheryas,
> >
> > Thanks - so are you saying that the PMF should be asymmetric with respect
> > to the leaflets even before I make the PMF symmetric? This seems to
> > contradict what Justin just said, but maybe you mean the same thing?
>
> I think we're saying the same thing, but I must correct an error I made.
> I misremembered the WHAM option you need. It is not -sym (which
> symmetrizes around zero), you need -cycl, which sets the end points to
> be equivalent. This is effectively "symmetry" but with respect to the
> end points, as I have been saying, rather than symmetry in the sense of
> a "mirror image" at equivalent +/- values of the reaction coordinate.
>
> -Justin
>
> > Den ons 21 nov. 2018 kl 14:57 skrev Shreyas Kaptan <
> shreyaskaptan at gmail.com
> >> :
> >> I am reasonably sure that if the bilayer composition is asymmetric with
> >> respect to leaflets you should see asymmetry in the PMF. In the ideal
> case,
> >> of infinite sampling, you should have zero free energy difference in the
> >> bulk solvent for either side.
> >>
> >> On Wed, Nov 21, 2018 at 2:52 PM Gmx QA <gmxquestions at gmail.com> wrote:
> >>
> >>> Thanks again,
> >>>
> >>> So then to summarize: Using -sym is appropriate in this case, even
> though
> >>> the bilayer is asymmetric with respect to lipid composition.  This fact
> >>> would show up anyway (in the limit of unlimited sampling?)
> >>>
> >>>
> >>>
> >>> Den ons 21 nov. 2018 kl 14:44 skrev Justin Lemkul <jalemkul at vt.edu>:
> >>>
> >>>>
> >>>> On 11/21/18 8:39 AM, Per Larsson wrote:
> >>>>> Hi,
> >>>>>
> >>>>> Thanks Justin, but shouldn't the PMF be (more or less) symmetric
> >>> anyway,
> >>>>> given the inherent bilayer symmetry?
> >>>>> In this case I have designed the two leaflets in the bilayer to have
> >>>>> non-identical lipid composition, so then I think using -sym would
> >>>>> obliterate any differences between the leaflets, no?
> >>>> No, because that's completely unknown (and irrelevant) to WHAM. It
> sets
> >>>> the leftmost window to a zero energy and calculates every window's
> >>>> energy relative to that, so you'll get the steady increase you see. If
> >>>> you tell it that the leftmost and rightmost windows are equal (which
> >>>> -sym), then the calculation proceeds differently.
> >>>>
> >>>> -Justin
> >>>>
> >>>>>
> >>>>>
> >>>>> On Wed, Nov 21, 2018 at 2:24 PM Justin Lemkul <jalemkul at vt.edu>
> >> wrote:
> >>>>>> On 11/21/18 7:22 AM, Gmx QA wrote:
> >>>>>>> Hi all gmx-users
> >>>>>>>
> >>>>>>> I am working on calculating the PMF using umbrella sampling of a
> >>>> (rather
> >>>>>>> large) molecule across a lipid bilayer. I have set up my umbrellas
> >>>> with a
> >>>>>>> 0,2 nm spacing, and run each window for 100 ns.
> >>>>>>>
> >>>>>>> The problem is that the resulting PMF is not symmetric with respect
> >>> to
> >>>>>> the
> >>>>>>> bilayer center. Initially is looks ok, but when the molecule is
> >>> exiting
> >>>>>> the
> >>>>>>> bilayer on the other side again, the PMF does not go back to
> >>> (roughly)
> >>>>>> the
> >>>>>>> same value as before entering the bilayer.
> >>>>>>>
> >>>>>>> I have uploaded the PMF file here:
> >>>>>>> https://files.fm/u/7ec2rshc
> >>>>>> You didn't get a symmetric profile because you didn't ask for one.
> >> Use
> >>>>>> the -sym option.
> >>>>>>
> >>>>>> -Justin
> >>>>>>
> >>>>>>> Any comments or suggestions are much appreciated. I understand the
> >>>>>> problems
> >>>>>>> and issues about calculations of a converged PMF with larger
> >>> molecules,
> >>>>>> but
> >>>>>>> nevertheless I would have expected my PMF to be symmetric, albeit
> >>>> perhaps
> >>>>>>> not converged.
> >>>>>>>
> >>>>>>> Thanks
> >>>>>>> /PK
> >>>>>> --
> >>>>>> ==================================================
> >>>>>>
> >>>>>> Justin A. Lemkul, Ph.D.
> >>>>>> Assistant Professor
> >>>>>> Office: 301 Fralin Hall
> >>>>>> Lab: 303 Engel Hall
> >>>>>>
> >>>>>> Virginia Tech Department of Biochemistry
> >>>>>> 340 West Campus Dr.
> >>>>>> Blacksburg, VA 24061
> >>>>>>
> >>>>>> jalemkul at vt.edu | (540) 231-3129
> >>>>>> http://www.thelemkullab.com
> >>>>>>
> >>>>>> ==================================================
> >>>>>>
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> >> --
> >> Shreyas Sanjay Kaptan
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> --
> ==================================================
>
> Justin A. Lemkul, Ph.D.
> Assistant Professor
> Office: 301 Fralin Hall
> Lab: 303 Engel Hall
>
> Virginia Tech Department of Biochemistry
> 340 West Campus Dr.
> Blacksburg, VA 24061
>
> jalemkul at vt.edu | (540) 231-3129
> http://www.thelemkullab.com
>
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