[gmx-users] Gibbs free energy landscape Vs. the stability of protein structure

[David van der Spoel]

On 22/09/15 07:42, Naba wrote:
> Thank you Justin. I have to deduce some inference from this figure. Please
> make me out about the following queries.
>
> On Mon, Sep 21, 2015 at 5:48 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>>
>> On 9/21/15 4:00 AM, Naba wrote:
>>
>>> Dear Gromacs users and Developers,
>>>
>>> I have performed dihedral PCA for 4 extracellular loops of a transmembrane
>>> protein after successfully finishing 100 ns of simulation at 300 and 310
>>> K.
>>> I obtained figures for each loops for two different temperatures as in
>>> this
>>> link: http://s28.postimg.org/dlva5i42l/d_PCA.jpg .
>>>
>>> As we can see in that figure that, the loop L1 has got only one minimum at
>>> both temperatures, whereas, L2 and L3 have got 4 minima at 300 K. I have
>>> also calculated the amount of frames in percentages at their respective
>>> minima. It seems that L2 and L3 have got more number of frames at their
>>> minima when combined in comparison to L1. Now my question is:
>>>
>>> Can we say that L2 and L3 are tend to be more stable at 300K than that of
>>> L1 at the both temperatures?
>>>
>>
>> I wouldn't make any argument about "stability" here.
>
>
> Then what can be concluded from this figure? Please hint some possible
> explanations.
Dihedral PCA is tricky business. For instance the "volume" of phase 
space sampled in each grid point varies making it difficult to compare 
the probability per volume (which is related to the free energy).

The fact that the difference between 300K and 310K is so large proves 
your sampling is far from complete as well, so basically your results 
are inconclusive (e.g. you sample areas at 300K that you don't at 310K).
>
>
>> Conformational sampling, maybe, but the question is whether or not these
>> PCs are the same between the different simulations. If you're not
>> projecting one trajectory onto the other's eigenvectors, you're quite
>> possibly comparing apples and oranges.
>>
>
> The PCs are same for both simulations. I followed dPCA procedure as you
> have explained in http://www.gromacs.org/Documentation/How-tos/Dihedral_PCA
> . To obtained the 2D projections as in the link of the figure I issued the
> following command for each and every loops:
>
> g_anaeig -v eigenvec_L*.trr -f dangle_L*.trr -s resized_loop*.gro
> -first 1 -last 2 -2d 2dproj_1_2.xvg
>
> I think, I am comparing the same projections for both the simulations.
>
>
>>
>> -Justin
>>
>> --
>> ==================================================
>>
>> Justin A. Lemkul, Ph.D.
>> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>>
>> Department of Pharmaceutical Sciences
>> School of Pharmacy
>> Health Sciences Facility II, Room 629
>> University of Maryland, Baltimore
>> 20 Penn St.
>> Baltimore, MD 21201
>>
>> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
>> http://mackerell.umaryland.edu/~jalemkul
>>
>> ==================================================
>> --
>> Gromacs Users mailing list
>>
>> * Please search the archive at
>> http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before
>> posting!
>>
>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>>
>> * For (un)subscribe requests visit
>> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
>> send a mail to gmx-users-request at gromacs.org.
>>
>
>
>


-- 
David van der Spoel, Ph.D., Professor of Biology
Dept. of Cell & Molec. Biol., Uppsala University.
Box 596, 75124 Uppsala, Sweden. Phone:	+46184714205.
spoel at xray.bmc.uu.se    http://folding.bmc.uu.se