Florescent proteins designed entirely from scratch

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Anastassia

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Message 89563 - Posted: 16 Sep 2018, 2:44:49 UTC

Hi! I am a postdoc in the Baker lab and me and all co-authors wanted to thank you for your contribution the new Baker lab paper published in Nature this week! In that paper, we were able to design a new fluorescent protein completely from scratch, much smaller than the Green Fluorescent Protein that is traditionally used by researchers to visualise processes in cells.

The paper presents many “firsts” in computational protein design. It is the first de novo design of the beta-barrel fold (one of the most described fold in the past 35 years, yet mysterious until now). It is also the first de novo design of a protein tailored to bind a small-molecule, which requires very high accuracy in the placement of side chains on protein backbones assembled from scratch. Additionally, we could show that these new proteins could fold and function as expected in vivo! We hope that the advances described in the paper will further unable the de novo design of many biosensors and catalysts tailored for specific applications.

Thanks to all the Rosetta@home volunteers who contributed to the validation of our designed proteins and binding sites.

Here is the link to the IPD webpage that contains a copy of the paper. The work was also featured in the news articles below (the news in Science contains a video of one of our proteins glowing in living cells).

https://www.bakerlab.org/index.php/2018/09/12/de-novo-fluorescent-proteins/

https://cen.acs.org/physical-chemistry/periodic-table/Designer-protein-tackles-binding/96/i37
http://www.sciencemag.org/news/2018/09/watch-these-new-designer-proteins-light-when-they-hit-their-target
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Jim1348

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Message 89567 - Posted: 16 Sep 2018, 14:36:22 UTC - in response to Message 89563.  
Last modified: 16 Sep 2018, 14:37:48 UTC

That really should be placed (probably by the moderator) in a sticky entitled "Research Highlights" or something like that, so that it is easily accessible and does not get lost. A significant result like that can not be expected all the time, but it is very encouraging when it happens.

Thanks for the update.
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Profile [VENETO] boboviz

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Message 89569 - Posted: 16 Sep 2018, 18:18:20 UTC - in response to Message 89567.  

That really should be placed (probably by the moderator) in a sticky entitled "Research Highlights" or something like that, so that it is easily accessible and does not get lost. A significant result like that can not be expected all the time, but it is very encouraging when it happens.


+1
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Profile Jacques Laurence do Nascimento Silva
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Message 89660 - Posted: 29 Sep 2018, 12:55:52 UTC

This is really motivating, seeing that the project is generating results.
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Profile dcdc

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Message 89978 - Posted: 9 Dec 2018, 16:42:51 UTC
Last modified: 9 Dec 2018, 17:38:59 UTC

This sounds really exciting! Thanks for posting the update, Anastassia. Quick question - approximately how many models did you run on Rosetta@home for the validation process?

I fully agree that this forum needs a research highlights channel, or maybe they just need to be added to a thread in "News" that has links to all of the research posts?

Also, here are the formatted links:
https://www.bakerlab.org/index.php/2018/09/12/de-novo-fluorescent-proteins/
https://cen.acs.org/physical-chemistry/periodic-table/Designer-protein-tackles-binding/96/i37
http://www.sciencemag.org/news/2018/09/watch-these-new-designer-proteins-light-when-they-hit-their-target
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Trotador

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Message 89997 - Posted: 13 Dec 2018, 23:35:26 UTC

Congratulations!

Keep the good work!
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Anastassia

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Message 90004 - Posted: 16 Dec 2018, 4:01:23 UTC - in response to Message 89978.  

Thanks for the positive feedback! We ran validation on Rosetta@home for 60-70 models for the first part of the work (the design of the fold, experimenting with different approaches) then another 50 designs with ligand-binding cavity.
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Message boards : Rosetta@home Science : Florescent proteins designed entirely from scratch



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