Dear all people in the Rosetta@HOME community,

My name is Nobuyasu Koga. I'm working with my wife, Rie Koga, on "de novo design of protein structures" for 5 years.
Today, we're really happy to be able to announce our exciting achievements, which is reported in a research article titled
"Principles for designing ideal protein structures" in the journal Nature !!
http://www.nature.com/news/proteins-made-to-order-1.11767

Historically, there is only one protein structure that has been computationally designed from scratch,
which is Top7. This was designed in our lab 10 years ago. Until now, there is no other structure designed de novo, because it was extremely difficult to design protein structure from scratch.
Here, we've discovered the fundamental rules relating secondary structures to tertiary motifs.
Guided by the rules, we succeeded in designing five different topologies of protein structures from scratch with a systematic way !!
The design technology we developed in this paper should now lead us to custom-design functional protein structures for novel therapeutic and industrial needs:
we can design both structure and function from scratch without using naturally occurring proteins !

Computational resources from you all over the world was definitely essential to perform this work !!
We carried out structure prediction simulations on Rosetta@HOME to explore the energy landscapes of our designed sequences,
and we tested that our designed sequences have funnel-shaped energy landscapes leading into the designed structure.
Here, we show the result of the design Fold-III from our paper. See the lower figure.
In the energy landscape (left figure), each red dot is the lowest energy structure predicted by a Rosetta@Home volunteer.
The y-axis represents the Rosetta energy, and the x-axis shows how much your predicted structures match the designed structure (right figure).
You can see that some simulation trajectories reached at the energy minimum corresponding to the designed structure,
and at the same time, assembly of all red dots (your contributions) clearly uncover the global energy landscapes, which is funnel-shaped !!
All your contributions enabled us to explore the vast energy landscape !!,
We really thanks to everybody !!

Again, the energy landscapes were depicted literally with >100,000 volunteers.
I want to write down all of your names here !!, but this is impossible....you know.
So, here, I'd like to introduce folks who reached the lowest energy minimum for each design.

Fold-I : Aalelan (United States)
Fold-II : Jef (United States)
Fold-III : georgebg (Bulgaria)
Fold-IV: medvjet009(Czech Republic)
Fold-V : _2e_ Russia.

Thank you !! You are awesome !!

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Thanks for taking the time out from your research to post. It's always satisfying to know that the workunits we are crunching are being used in real breakthroughs.

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Thanks for the information!

I have one question though. In your post you say:

" The design technology we developed in this paper should now lead us to custom-design functional protein structures for novel therapeutic and industrial needs."

Can you give a more concrete example?
Can you (to give a random example) create proteins which can cure an autoimmune disorder?

I appreciate the effort you put into the post! :)

Thanks for taking the time out from your research to post. It's always satisfying to know that the workunits we are crunching are being used in real breakthroughs.

Big quote!

Thanks for the reply !!

It should be able to design protein binders to viruses or cancer related proteins for cure. I'm not expert on the autoimmune disorder, but it is highly possible to design novel medicine to inhibit/block the antibody that induce autoimmune disorder.

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Wow, that's AWESOME! you guys are getting my CPU power to deal with all of this!

Again, thanks for taking the time to visit this forum.

Thanks for the reply !!

It should be able to design protein binders to viruses or cancer related proteins for cure. I'm not expert on the autoimmune disorder, but it is highly possible to design novel medicine to inhibit/block the antibody that induce autoimmune disorder.

we succeeded in designing five different topologies of protein structures from scratch with a systematic way !!

Nobuyasu Koga

Plz, explain when the 5 proteins was created and when they was tested on Rosetta@home like what month and year. Thanks so much and Gratz for making this possible.

Tom Zolotor

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Hi, Tom

Date for computationally created and tested on Rosetta@HOME are

Fold-I : 03/10/2011
Fold-II : 01/30/2012
Fold-III: 06/13/2011
Fold-IV: 10/17/2011
Fold-V : 08/14/2011

Date for experimentally determined by NMR:

Fold-I : 06/30/2009
Fold-II : 06/29/2012
Fold-III: 12/15/2011
Fold-IV: 06/30/2012
Fold-V : 05/15/2012

Actually, the energy landscape of Fold-I were resampled after when we experimentally determined the structure, because the Rosetta potential functions were changed. That's why the tested date on Rosetta@HOME is after the experimentally determined date.
As I remember, the first time when we tested for Fold-I was probably 2008. But I don't have a exact record for that time. Sorry.

Currently, we're designing bigger proteins of which residues are more than > 100 !
This is a certainly big step for us. You know our designed proteins were less than 100.
How big proteins we can design ? Can we apply the same rules for designing bigger proteins ?
I hope I can update great news soon !

thanks !

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Thank you so much for posting here and coming back to answer our questions. In another thread someone asked what can be done to increase volunteer participation in rosetta@home. I think it's exactly this sort of information that can help. It's not just the announcement of papers published (which are difficult for most of us to read and understand) but a brief layman's explanation coupled with the sorts of details that help us place our contribution within the larger context.


Best,
Snags

p.s. Please encourage your colleagues to post as well. They don't need to, in fact shouldn't, wait until they have a paper to publish to let us know what they/we are working on.

Hi, Tom

Date for computationally created and tested on Rosetta@HOME are

Fold-I : 03/10/2011
Fold-II : 01/30/2012
Fold-III: 06/13/2011
Fold-IV: 10/17/2011
Fold-V : 08/14/2011

Date for experimentally determined by NMR:

Fold-I : 06/30/2009
Fold-II : 06/29/2012
Fold-III: 12/15/2011
Fold-IV: 06/30/2012
Fold-V : 05/15/2012

Actually, the energy landscape of Fold-I were resampled after when we experimentally determined the structure, because the Rosetta potential functions were changed. That's why the tested date on Rosetta@HOME is after the experimentally determined date.
As I remember, the first time when we tested for Fold-I was probably 2008. But I don't have a exact record for that time. Sorry.

Currently, we're designing bigger proteins of which residues are more than > 100 !
This is a certainly big step for us. You know our designed proteins were less than 100.
How big proteins we can design ? Can we apply the same rules for designing bigger proteins ?
I hope I can update great news soon !

thanks !

Thanks so much for giving the dates, Nobuyasu Koga, we are so glad you and your wife have done something that will help science. We are in your debt! As an astronomer, I love scientific discoveries. Keep up the good work!

Tom Zolotor

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Hi, Tom

Date for computationally created and tested on Rosetta@HOME are

Fold-I : 03/10/2011
Fold-II : 01/30/2012
Fold-III: 06/13/2011
Fold-IV: 10/17/2011
Fold-V : 08/14/2011

Date for experimentally determined by NMR:

Fold-I : 06/30/2009
Fold-II : 06/29/2012
Fold-III: 12/15/2011
Fold-IV: 06/30/2012
Fold-V : 05/15/2012

Actually, the energy landscape of Fold-I were resampled after when we experimentally determined the structure, because the Rosetta potential functions were changed. That's why the tested date on Rosetta@HOME is after the experimentally determined date.
As I remember, the first time when we tested for Fold-I was probably 2008. But I don't have a exact record for that time. Sorry.

Currently, we're designing bigger proteins of which residues are more than > 100 !
This is a certainly big step for us. You know our designed proteins were less than 100.
How big proteins we can design ? Can we apply the same rules for designing bigger proteins ?
I hope I can update great news soon !

thanks !

Nobuyasu Koga


When Fold-I was released on 03/10/2011 was it tested on rosetta@home for several months after release?

Thanks,
Tom Zolotor

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Hi, Tom

W've tested Fold-I twice: before and after the release date, 06/30/2009.
One is in 2008, and the other is 03/10/2011.
This is because the rosetta parameters was changed, so we tested it again.

best.
Nobuyasu Koga

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Hi, Tom

W've tested Fold-I twice: before and after the release date, 06/30/2009.
One is in 2008, and the other is 03/10/2011.
This is because the rosetta parameters was changed, so we tested it again.

best.
Nobuyasu Koga

Was Fold-I tested only on one date or day or several months from the 2nd release date of 03/10/2011. I joined Rosetta april 28th of 2011 and was wondering if Fold-I was still being re-tested then?

Thanks.
Tom

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Hi, Tom

Fold-I was tested only on the day: 03/10/2011, and the work units at that time have been distributed within a few days.

thanks !