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Message boards : News : New paper: Characterization of partially ordered states in the intrinsically disordered N-terminal domain of p53 using millisecond molecular dynamics simulations

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Toni
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Message 55189 - Posted: 26 Aug 2020 | 11:11:54 UTC
Last modified: 26 Aug 2020 | 17:04:46 UTC

The latest scientific publication obtained with your support and computation is here:

Herrera-Nieto, P., Pérez, A. & De Fabritiis, G. Characterization of partially ordered states in the intrinsically disordered N-terminal domain of p53 using millisecond molecular dynamics simulations. Sci Rep 10, 12402 (2020).

It investigates an open and difficult problem in biology, namely the structure-function relationship of intrinsically disordered proteins (IDP). IDP proteins are involved in many regulatory processes, and yet are difficult to study both experimentally and computationally. The amount of power provided by GPUGRID volunteers came to the rescue, enabling very extensive sampling of p53, an exemplary IDP involved in oncogenic processes.



The exploration of intrinsically disordered proteins in isolation is a crucial step to understand their complex dynamical behavior. In particular, the emergence of partially ordered states has not been explored in depth. The experimental characterization of such partially ordered states remains elusive due to their transient nature. Molecular dynamics mitigates this limitation thanks to its capability to explore biologically relevant timescales while retaining atomistic resolution. Here, millisecond unbiased molecular dynamics simulations were performed in the exemplar N-terminal region of p53. In combination with state-of-the-art Markov state models, simulations revealed the existence of several partially ordered states accounting for ∼ 40% of the equilibrium population. Some of the most relevant states feature helical conformations similar to the bound structure of p53 to Mdm2, as well as novel 𝛽-sheet elements. This highlights the potential complexity underlying the energy surface of intrinsically disordered proteins.

Thomas H.V. DUPONT
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Message 55190 - Posted: 26 Aug 2020 | 11:17:15 UTC

Nice!
Thanks for the heads-up, Toni!
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[CSF] Thomas H.V. Dupont
Founder of the team CRUNCHERS SANS FRONTIERES
www.crunchersansfrontieres.org

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Message 55191 - Posted: 26 Aug 2020 | 14:26:46 UTC

Congrats to the team and my fellow volunteers! ✨🥇✨
Another important step in understanding our molecular physiology completed.

And You Were There! (apologies to Walter Cronkite)

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Message 55192 - Posted: 26 Aug 2020 | 15:36:51 UTC

Congratulations!

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Message 55193 - Posted: 26 Aug 2020 | 20:01:12 UTC

Very nice!
Has a badge been assigned for this one already?

To my surprise I found two additional contribution badges for the following two publications - which apparently have not (yet?) been mentioned here in this news section:

1. Small Molecule Modulation of Intrinsically Disordered Proteins Using Molecular Dynamics Simulations
2. Computational and experimental characterization of NF023, a candidate anticancer compound inhibiting cIAP2/TRAF2 assembly

Michael.
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President of Rechenkraft.net - Germany's first and largest distributed computing organization.

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Message 55194 - Posted: 27 Aug 2020 | 5:28:06 UTC

Nice - congrats ...

But a "one-time-only" notice would suffice ...

Toni
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Message 55195 - Posted: 27 Aug 2020 | 14:29:17 UTC - in response to Message 55193.
Last modified: 27 Aug 2020 | 14:30:49 UTC

Has a badge been assigned for this one already?


Yes it has. Note that the WUs were done in the past so relatively new crunchers won't show up.



To my surprise I found two additional contribution badges for the following two publications - which apparently have not (yet?) been mentioned here in this news section:


Yes. I'll write up news gradually but badges are there already.


But a "one-time-only" notice would suffice ...


Where are you getting duplicate notifications?

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Message 55197 - Posted: 27 Aug 2020 | 18:41:59 UTC

I realize this is the wrong place to ask, but I haven't seen much talk about it elsewhere on the forum: am I supposed to still be getting WUs from GPUGrid or is the project no longer sending out work?

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Message 55198 - Posted: 27 Aug 2020 | 21:58:24 UTC - in response to Message 55197.

... or is the project no longer sending out work?

Maybe you are new to BOINC. But you check the server status page first.
http://www.gpugrid.net/server_status.php

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Message 55200 - Posted: 28 Aug 2020 | 13:13:52 UTC - in response to Message 55198.

Ah, ok. So no more currently queued up tasks. Is the project going onto a "permanent" hiatus like Seti@home or should I leave the project attached to my BOINC for future/upcoming WUs? :)

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Message 55202 - Posted: 28 Aug 2020 | 13:43:28 UTC - in response to Message 55200.
Last modified: 28 Aug 2020 | 13:51:53 UTC

Ah, ok. So no more currently queued up tasks. Is the project going onto a "permanent" hiatus like Seti@home or should I leave the project attached to my BOINC for future/upcoming WUs? :)


Work units are still being sent, but hard to get at the moment. Looking forward to a pickup in activity soon!

Toni posted this in regards to current status of project:
https://gpugrid.net/forum_thread.php?id=5154&nowrap=true#55196

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Message 55203 - Posted: 28 Aug 2020 | 15:09:11 UTC

They have just finished up two large runs, the biggest I have ever seen. It takes them a while to digest the results, write their papers, etc.
We will get more later, but I expect not for some time.

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Message 55205 - Posted: 30 Aug 2020 | 19:53:21 UTC

I can't download tasks? is this project finished or is the server being worked on? Thanks

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Message 55226 - Posted: 1 Sep 2020 | 21:06:36 UTC

Congratulations for your work and thank you for making us (a little) contribute to a better understanding of biology.

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Message 55228 - Posted: 1 Sep 2020 | 23:24:46 UTC

Wow! Another big run of MDADex2s WUs, folks.
Eres increíble, amigos.

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Message boards : News : New paper: Characterization of partially ordered states in the intrinsically disordered N-terminal domain of p53 using millisecond molecular dynamics simulations