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

[Naba]

Then, should I perform some more simulations at more different temperatures
or should I go for simulated annealing?
As of now, I actually have performed two simulations of each 100 ns at 300
and 310K only to differentiate two conditions. More elaborately speaking, I
have modeled the outermembrane protein and simulated it for 100 ns at 300K
in order to extrapolate as well as to validate the modeling protocol, which
I wanted to observe at 310K, i.e., at 37degree Celsius (so called "human
body temperature"). But as the replies imply that my sampling is not
completed what should be done in this case? Please suggest some comments.

On Tue, Sep 22, 2015 at 4:08 PM, David van der Spoel <spoel at xray.bmc.uu.se>
wrote:

> 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
>>>
>>> ==================================================
>>> --
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>>
>>
>>
>
> --
> 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
>
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-- 
Nabajyoti Goswami

Research Associate
Bioinformatics Infrastructure Facility
Department of Animal Biotechnology
College of Veterinary Science
Khanapara,Guwahati 781022
Assam, India