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

[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
>>>>>>
>>>>>> ==================================================
>>>>>>
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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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-- 
==================================================

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

==================================================