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

[Naba]

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: Loading Image... .

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?
Please help.
Thanks in advance.

Regards

Nabajyoti Goswami

College of Veterinary Science
Khanapara, Guwahati 781022
Assam, India.

[Justin Lemkul]

Post by Naba
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
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. 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.

-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

***@outerbanks.umaryland.edu | [phone]
http://mackerell.umaryland.edu/~jalemkul

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

[Naba]

Thank you Justin. I have to deduce some inference from this figure. Please
make me out about the following queries.

Post by Justin Lemkul

Post by Naba
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
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.

Post by Justin Lemkul
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.

Post by Justin Lemkul
-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
http://mackerell.umaryland.edu/~jalemkul
==================================================
--
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--
Nabajyoti Goswami

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

[David van der Spoel]

Post by Naba
Thank you Justin. I have to deduce some inference from this figure. Please
make me out about the following queries.

Post by Justin Lemkul

Post by Naba
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
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).

Post by Naba

Post by Justin Lemkul
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
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.

Post by Justin Lemkul
-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
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
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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: [phone].
***@xray.bmc.uu.se http://folding.bmc.uu.se

[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.

Post by Naba
Thank you Justin. I have to deduce some inference from this figure. Please
make me out about the following queries.

Post by Naba
Dear Gromacs users and Developers,

Post by Naba
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
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).

Post by Naba
Conformational sampling, maybe, but the question is whether or not these

Post by Naba
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
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.

Post by Naba
-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
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

--
David van der Spoel, Ph.D., Professor of Biology
Dept. of Cell & Molec. Biol., Uppsala University.
Box 596, 75124 Uppsala, Sweden. Phone: [phone].
--
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

--
Nabajyoti Goswami

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

[Padmani Sandhu]

Hello justin,

Thanks, actually I want to study movement of protons along the lenght of a
water channel.


Regards,


Padmani

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--
*Padmani sandhu*
*Research Scholar,*
*Center for Computational Biology and Bioinformatics,*
*Central University of Himachal Pradesh,*
*Temporary Academic Block, Shahpur *
*Pin 176206, District Kangra,*
*Himachal Pradesh, India*

[Padmani Sandhu]

Sorry, I have posted my reply in wrong thread.

Post by Padmani Sandhu
Hello justin,
Thanks, actually I want to study movement of protons along the lenght of a
water channel.
Regards,
Padmani

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--
*Padmani sandhu*
*Research Scholar,*
*Center for Computational Biology and Bioinformatics,*
*Central University of Himachal Pradesh,*
*Temporary Academic Block, Shahpur *
*Pin 176206, District Kangra,*
*Himachal Pradesh, India*

--
*Padmani sandhu*
*Research Scholar,*
*Center for Computational Biology and Bioinformatics,*
*Central University of Himachal Pradesh,*
*Temporary Academic Block, Shahpur *
*Pin 176206, District Kangra,*
*Himachal Pradesh, India*