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

Wed Nov 21 18:22:27 CET 2018

Hi PK,

I just looked at your PMF profile.xvg - you have a huge offset between 
the left and right end (140 kJ/mol), suggesting that you have a major 
problem with convergence. I would not use -cycl here - as such, I 
disagree here with the previous messages. :)

-cycl is acceptable if your PMF looks more or less cyclic (no offset 
between left and right end). In that case, -cycl makes use of your 
knowledge that the PMF "should" be cyclic if you would simulate much 
longer. In other words: Witih -cycl, you get the most plausible PMF in 
the light of (i) your histograms and (ii) your knowledge that the PMF 
should be cyclic.

I would instead try to find out *why* you have such a massive sampling 
problem. A reason could be that you have not used a good reaction 
coordinate (probably the COM of the solute wrt. the membrane?). Maybe 
you drag a lot of water into the membrane in the xi<0 region, but not in 
the x>0 region?

Good luck,
Jochen

Am 21.11.18 um 15:49 schrieb Justin Lemkul:
> 
> 
> 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
>>>>>>>
>>>>>>> ==================================================
>>>>>>>
>>>>>>> -- 
>>>>>>> Gromacs Users mailing list
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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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>>>
>>> -- 
>>> Shreyas Sanjay Kaptan
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-- 
---------------------------------------------------
Dr. Jochen Hub
Computational Molecular Biophysics Group
Institute for Microbiology and Genetics
Georg-August-University of Göttingen
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Phone: +49-551-39-14189
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