[Rosetta@Home] Nieuws updates

[Kristof]

Blijkbaar wordt er aangemoedigd om nieuws updates te scheiden van de DPCHs.
Bij deze zal ik vanaf nu alle nieuwsupdates aan dit topic toevoegen.
Reacties hierop zijn uiteraard ook steeds welkom.

[Kristof]

In zijn journal schreef David Baker (voor diegene die hem nog niet kennen: Scientist en Developper bij Rosetta) hetvolgende:

I met today with Dr. Wayne C. Koff, the Senior Vice President for Vaccine Research at the
International AIDS Vaccine Initiative (IAVI). You can read about IAVI at http://www.iavi.org/.
We have recently joined the team of researchers they are supporting to collaboratively work towards a vaccine, and we discussed many different strategies and the ways in which we can work most productively with other IAVI vaccine developers.

On a different front, I gave the opening keynote talk at a chemical engineering meeting on creating new biological molecules and systems earlier this week in San Diego. Our computational approaches are very complementary to the experimental approaches developed by chemical engineers, and in discussions over the next two days I established a number of very exciting collaborations on creating new drugs and enzymes for many applications. You can read about the meeting at http://www.aiche.org/sbe/events/ICBE/program.aspx. (you will see that the keynote speaker the second night was Craig Venter, who led the private efforts to sequence the human genome--he gave a quite futuristic talk on creating brand new organisms).

[ Voor 5% gewijzigd door Kristof op 19-01-2007 13:16 ]

[Kristof]

Jan 29, 2007
Rosetta@home has been updated to version 5.45. The new version has some fixes in the graphics to make it significantly more stable and, as a result, sidechains and protein rotation has been turned back on. Some science related updates are also included. For details, see this thread.

David Kim weet er volgende informatie nog bij te geven:

Rosetta version 5.45

In this release, we've made some bug fixes in the graphics and have turned the display of sidechains and mouse rotation of the protein back on. We are hoping the graphics in this release are significantly more stable.

There are also some minor modifications in the science code.

edit:

I almost forgot to mention that we've also started using UPX (http://upx.sourceforge.net/ to compress the windows and linux executables. The result is a 3 fold reduction in the size of the windows app and 2 fold for linux. We'd like to thank Rytis Slatkevicius for suggesting UPX.

[Bio1ogics]

Die nieuwe versies worden toch vanzelf ge-update, kristof?

[Kristof]

Bio1ogics schreef op dinsdag 30 januari 2007 @ 08:02:
Die nieuwe versies worden toch vanzelf ge-update, kristof?

Klopt! Je client zal deze automatisch binnenhalen bij de volgende keer dat je results upload en nieuwe jobs binnenhaalt.
Bovenstaande post is enkel ter informatie wat er aan de client verandert.

[Kristof]

Een nieuwe update van de journal van Baker:

We are just finalizing two manuscripts which describe some of the most exciting results obtained thus far by rosetta@home. We have identified the rosetta@home contributors who found the rather spectacular low energy structures reported in the first paper, and would like to acknowledge them in the paper. Our question is whether to acknowledge these contributions through usernames or real names, and we certainly don't want to use the latter without permission. Here are the user names of the four participants for the first paper, I'll post the participants we would like to acknowledge in the second paper when we have identified them.

78884 aotama
66651 DJ N-4ceR
77194 DOJ F@T Elvis Clan
49841 S-A-M

It would be great if the above participants could let us know how they would like to be acknowledged.

[Mobster]

Als ze er nu bij zetten bij welk team ze zitten. Dan kunnen de fanatiekelingen binnen hun forum de boel uitzoeken. Mij zeggen deze nicks niks Geen DPC-ers volgens mij.

[TheZoo]

Misschien iemand die niets te doen heeft en dit gaat uitzoeken?

[Kristof]

Vandaag mag ik nog eens nieuws aankondigen van David zijn Journal.
Deze keer heb ik echter beter nieuws.
Ik heb op zijn minst 1 DPC'er gevonden die het vermelden waard is. (Zie vetgedrukte naam)
Als er nog mensen zijn die iemand anders herkennen?
edit: 2de gevonden

Yesterday I acknowledged the participants who found the low energy structures being reported in Rhiju's paper. Today I have a list of the participants who found the low energy structures for the proteins reported in Bin's paper (the list is longer because Bin's paper describes a number of different proteins, we are citing the four participants who found the lowest energy structures for each of them). Again, please let us know how you would like to be acknowledged.

33706 gibsonrr
22840 Jynxedu
93320 John Michael Hess
59655 Luke

66275 Marko
757 Ian_D
82740 pxee
42892 csbyrosetta

96970 Allan Staib
97036 TJSwan
80380 Yunomi
7028 Etienne Guyot

31134 GeorgeF
68333 Jarom Smith
9221 UBT - Menace
62362 Boštjan Rudolf

17199 [SETI.USA] D. Brown
90304 bs98909
86711 papagoof
76056 Ackiss

86743 Noel E. Shea
58129 Bjarke.Orbeck
2446 SerVal
55755 Erik

33464 [DPC]FOKschaap~devzero
44026 A's Team
13172 jeidler
9030 Rebel Alliance

[TheZoo]

Kristof schreef op dinsdag 06 februari 2007 @ 11:28:
Ik heb op zijn minst 1 DPC'er gevonden die het vermelden waard is. (Zie vetgedrukte naam)

Nounou zeg, dat was een hoop werk om die te vinden...............

[devzero642]

heeft het toch nog nut gehad

[Kristof]

Er is een 2de DPC'er gevonden, met name Eric

[Kristof]

Er is een nieuwe versie van de Rosetta client verschenen. Naar gewoonte zal deze automatisch binnenkomen bij het volgende contact met de server. Je hoeft er dus niets voor te doen, maar toch hier de details ter informatie:

Rosetta version 5.46

In this release, we've fixed the bug observed in V5.45 which has caused a high rate of "watchdog termination" for workunits, especially docking ones "DOC..." Please note that even with the fix, watchdog errors can still be seen sometimes and that is because Rosetta simulations get stuck during searching large, complicatined energy landscape, but this should happen randomly at a very low rate.

There are also some minor modifications in the science code.

[Kristof]

Uit het Journal van David Baker:

I only ended up hearing from 3 contributors, who are acknowledged by their real names in the papers we just submitted to Science; the others are acknowledged through their user names. There is still a month or so during which we can substitute in real names if we hear from you.

In other developments, inspired by a discussion with my 12 year old son Benjamin, we have started to look hard at how to improve on the carbon sequestration activity of the plant enzyme rubisco. there are many exciting applications in this area, ranging from biofuels to attempting to counteract global warming by reducing C02 levels in the atmosphere. I hope to have experiments up and running on rubisco within a month or two, and to start generating and testing computational designs of improved rubiscos (which all of you will be able to work on) not too long after that. The HIV vaccine design project is running full speed, with many potential vaccines being tested as I type, so we have some time now to get up to speed on the next big challenge!

[ Voor 0% gewijzigd door Kristof op 15-02-2007 14:37 . Reden: typo ]

[Kristof]

De inmiddels beruchte én bekende David Baker had hetvolgende toe te voegen aan zijn inmiddels even beruchte én beroemde Journal:

One of the key advances that underlies our HIV vaccine design efforts has recently been published in the scientific journal Nature by the research group of Dr. Peter Kwong, with whom we are collaborating closely. Dr. Kwong's group has determined how an antibody can neutralize the virus by binding to a critical region on its surface required for binding to and entering our cells. We have been using the newly published structure, which Dr. Kwong made available to us many months ago, to design small protein mimics of the virus that we hope will elicit similar antibodies when people are vaccinated with them. You can read about Dr. Kwong's discoveries by picking up Nature at a newstand (his work was featured on the cover!) or from the press releases; I'm pasting the first part of one of these below:

Scientists Unveil Piece of HIV Protein that May Be Key to AIDS Vaccine Development
In a finding that could have profound implications for AIDS vaccine design, researchers led by a team at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), have generated an atomic-level picture of a key portion of an HIV surface protein as it looks when bound to an infection-fighting antibody. Unlike much of the constantly mutating virus, this protein component is stable and — more importantly, say the researchers — appears vulnerable to attack from this specific antibody, known as b12, that can broadly neutralize HIV.

“Creating an HIV vaccine is one of the great scientific challenges of our time,” says NIH Director Elias A. Zerhouni, M.D. “NIH researchers and their colleagues have revealed a gap in HIV’s armor and have thereby opened a new avenue to meeting that challenge.”

The research team was led by Peter Kwong, Ph.D., of NIAID’s Vaccine Research Center (VRC). His collaborators included other scientists from NIAID and the National Cancer Institute, NIH, as well as investigators from the Dana-Farber Cancer Institute, Boston, and The Scripps Research Institute in La Jolla, CA. Their paper appears in the February 15 issue of Nature and is now available online.

“This elegant work by Dr. Kwong and his colleagues provides us with a long-sought picture of the precise interaction between the HIV gp120 surface protein and this neutralizing antibody,” says NIAID Director Anthony S. Fauci, M.D. “This finding could help in the development of an HIV vaccine capable of eliciting a robust antibody response.”

[Kristof]

Door afwezigheid heb ik enkele dagen gemist. Bij deze een update:

Mar 1, 2007
Rosetta@home has been updated to version 5.48. We are including a special symmetric docking protocol and a fix to the problem of frequent watchdog terminations of docking workunits. For details, see this thread.

en

Mar 2, 2007
See David Baker's recent journal post describing plans to use Rosetta@home to computationally design enzymes for simplified biochemical cycles that sequester carbon from CO2.

In de journal waarnaar verwezen wordt, vind je:

We have spent the last several days devising simplified biochemical cycles that would convert carbon dioxide into simple sugars using enzymes we would computationally engineer with your help on rosetta@home. Graduate student Justin Siegal and postdoc Eric Althoff have come up with a very clever new reaction cycle using new enzymes we would collectively engineer that in total carries out the following reaction:

2C02 + 2e- + H20 -> C2O3H2 + O2

the product is a simple sugar that could be used in a variety of ways, and the removal of C02 from the atmosphere would be great for countering global warming. A nice thing about this compared to current ideas of forming inorganic carbonate compounds is that it requires no other inputs. However, it does require electrons, and hence a source of energy. We are currently assessing the energy requirements of this process and comparing them to those of other proposed carbon sequestration mechanisms.

en

Our HIV vaccine design efforts are now going full speed ahead after months of building up after our Gates foundation award began in August. There are now seven full time exceptionally talented scientists working on the project, and we are exploring a broad range of strategies. Because computational protein design has never been applied to vaccine design before, our efforts have been very enthusiastically recieved by the community of scientists working on HIV vaccine design problem, and we are now collaborating with many of the most active research groups in this area and recently joined the Neutralizing Antibody Consortium (http://www.iavireport.org/Issues/0602/Neuts.asp). We are very much hoping our new computational methodology can contribute to a breakthrough in this critical area!

en

I would like to apologize for the recent problems many participants had which were due to the filling of the rosetta@home queue with the memory intensive "HINGE" workunits. With these work units we were building models for the current CAPRI protein-protein structure prediction challenge http://capri.ebi.ac.uk/, for which predictions must be submitted by Sunday, and so the jobs were targeted as high priority. The problem was that while we specified a minimum of 512MB of memory for these jobs, this was only sufficient for many of your machines if only a single CPU was being used. Once again, we apologize for the problems which the combination of high memory and high priority caused, and will definitely avoid this in the future.
[I'm posting this here for people who didn't see the thread where the problem was discussed]

[Kristof]

En Rosetta gaat maar door. Alweer een nieuwe client update, die deze keer voor de crunchers een extraatje biedt:

Rosetta@home has been updated to version 5.51 -- our first update after CAPRI. This version has a nifty new 'cartoon' look for graphics. We'll also be testing a new mode to predict structures of RNA, an older cousin of DNA, that folds into interesting unique structures.


Rosetta@home is at version 5.51 with some new features!

1. The style of graphics has been updated to use a "cartoon" representation of the backbone. This format has ribbons for alpha helices and arrows from beta strands, and was popularized by Jane Richardson and others in the 1980s. Its the style that we actually use to visualize and assess structures in the lab, and the style most commonly used for scientific publication.

2. There are some "easter eggs" -- you can change the color of sidechains from the keyboard if you view Rosetta@home from the BOINC Manager (show graphics) rather than as a screen saver.

3. A new mode of Rosetta has been implemented that carries out structure prediction for ribonucleic acid (RNA), which is thought to be dominant biopolymer at early stages of life, back before there was DNA and proteins.

[Kristof]

Er is een update van de Rosetta-applicatie doorgevoerd. Je hoeft er zoals altijd niets voor te doen, deze wordt automatisch gedownload als je devolgende keer contact maakt met de server.
De details:

Rosetta@home is now updated to version 5.54. The main features are:

1. RNA modes should now correctly crunch though as many workunits as your CPU run time preference allows (typically 4 hours), instead of always trying to do 30 structures.

2. A few glitches in the graphics have been fixed. In particular, a small fraction of users reported problems with crashes. In this update, we've tried to make the code more robust, so please let us know here if you cannot see graphics consistently.

[Kristof]

Rhiju geeft wat meer uitleg over de jobs die momenteel op jullie koetjes draaien:

The work units labeled RNA_ABINITIO model folding of small chains of RNA, a molecule similar to DNA. They start from extended chains and then try to maximize the pairing and stacking of the RNA sidechains ("bases").

Info on where the sequences come from:

1a4d
E-loop from ribosome 5S RNA

1esy
HIV psiRNA dimerization signal

1kka
tRNA anticodon stem loop

1l2x and 2a43
Viral frameshifting pseudoknots

1qwa
Nucleolin binding hairpin

1q9a
Sarcin/ricin loop from the large ribosomal subunit

1zih
GNRA tetraloop

2f88
Domain I from the self-splicing Group II intron

1xjr
Rigorously conserved RNA element from SARS

1ehz
tRNA(phe) from yeast

1gid
The P4-P6 domain from the self-splicing Tetrahymena group I ribozyme

En Ingemar, een andere wetenscahpper aldaar, voegt er aan toe:

Jobs with names DOCKING_*rhj* is running protein-protein docking on dimers where the individual monomers are related by symmetry. The structures are coming from ab-initio structure prediction. The structure of this protein could not be solved by standard techniques used for determining crystal structures. Although a crystal could be grown and experimental data looks good one of the procdures in crystal structure determination, phasing, could not succesfully be carried out starting from similar proteins previously solved. The idea here is to create models with ab-intio+docking that can be used as starting points for the phasing procedure. If this works this could be way of rescuing data from x-ray crystallography data from biologically important proteins that can not be converted to 3D-structures, which would a significant breakthrough.

Thanks for your help!

[Kristof]

En een nieuw nieuwtje. Volgens David is het 'exciting' nieuws

Lots of exciting things happening now!

The entire HIV vaccine design team (close to ten people now!) went to a meeting near Vancouver last week and were delighted at the enthusiasm their application of computational methods to vaccine design is generating in the field. Now, in collaboration with the many research groups we are working with, we just have to come through with vaccine candidates that elicit a neutralizaing response to HIV!

Paul Murphy, a graduate student in the group, is working on a project I haven't described previously which may interest many of you. As you might know, many human diseases caused by mutations in specific genes can potentially be cured by introducing stem cells that have the mutation fixed. The problem has been that in some cases the stem cells can divide too much which can lead to tumors. So what is necessary is a way to kill the introduced cells if things go wrong with the therapy. Paul's approach is to take advantage of an anti fungal drug -- 5 fluoro cytosine -- which is not itself toxic
but is converted by an enzyme present in fungi, but not in human cells, to a toxic compound. Paul is working to redesign a human enzyme to catalyze this reaction, if he succeeds, this enzyme could be included in the introduced cells so that they can be specifically killed by the drug if necessary. (simply putting the fungal enzyme into the cells is not good because it will be recognized as foreign by the immune system).

Finally, welcome to the ESL team which has given us a much needed surge in computing power this past week!

[Kristof]

En een nieuwe build van de Rosetta engine:

Rosetta@home is at version 5.59. There are several new features:

1. There were issues for Rosetta@home on a small fraction of Macs for the last couple updates. This appears to be fixed. Thanks to all the Mac users who posted here, attached their computers to Ralph, and helped us resolve this issue!

2. The "percentage complete" steadily increases every five seconds during the workunit. It should be reasonably accurate except in the occasional workunit that goes a little over your preferred CPU run time; this happens when your workunit has an exceptionally promising score, and Rosetta decides to continue crunching. In those cases, the percentage complete is slowly updated so that the estimated time to completion stays around 10 minutes.

3. The "estimated time to completion" is occasionally a little off at the beginning of the workunit; no need to worry about it!

4. We have implemented a more accurate energy function for RNA, thanks to your efforts with the previous apps.

5. We have implemented a new mode of Rosetta that simultaneously simulates folding and docking of two symmetric chains. This was inspired by a protein whose crystallographic data we are trying to "phase" as well as the many proteins in Nature that form symmetric dimers.

Zoals steeds enkel ter info, want hij zal automatisch binnen komen

en nog een update van de WUs die momenteel draaien. Er is er een nieuwe bijgekomen:

We're running a new kind of workunit with the tag SYMM_FOLD_AND_DOCK in the names. These are some pretty crazy jobs -- you'll see two protein chains shaking and dancing around each other. We're trying to predict structures of proteins that form symmetric multimers (a category that includes many many proteins including virus coats and proteins that modulate DNA transcription). Previously you've seen straight folding of one chain, and docking of two structured chains, but this is the first time we're simultaneously exploring the fold and the relative orientation of the chains. This is a huge conformational space to explore, and is onl possible with Rosetta@home.

A first application of this new protocol is to a structural genomics target (s036) for the purpose of "phasing" crystallographic data -- see the post by Ingemar below.

[ Voor 25% gewijzigd door Kristof op 04-04-2007 07:31 ]

[Kristof]

Na een tijdje nieuwsstilte, is volge'nde verschenen op de frontpage:

We are starting to post Top Prediction images again, starting with a few RNA structures. Congratulations to Mika Immonen (Team AncientGods Distributed Computing) for predicting the lowest energy structure for the RNA 283d!

In het journal van David Baker is hetvolgende terug te vinden:

As I have described previously, we are working toward developing agents for gene
therapy by redesigning homing endonucleases (DNA cleavage enzymes) to
cut within genes containing mutations responsible for various
diseases. It has been shown that cleavage near a disease-causing
mutation will induce cellular recombination pathways leading to
correction of that mutation. Our focus is on diseases amenable to
gene therapy, where the healthy cells have an advantage over the
diseased cells, and correction of the genomes of even a fraction of
the cells can cure the disease. The diseases on our list include (but
not limited too), fanconi anemia, cystic fibrosis, haemophila A,
XSCID, ADASCID, and tyrosinemia I. Recently, we have produced
successful endonuclease designs toward partial target sequences near
mutations in genes responsible for fanconi anemia, haemophilia A, and
tyrosinemia I, bringing us steps closer to our goal of developing proteins
that can help cure these diseases.

We are all excited about the increase in computational throughput in the last month which
is letting us test many more ideas more quicly. Thanks to all of you!

[Kristof]

Exact 1 maand na de vorige client-update, weet David Kim ons te vertellen dat er een nieuwe client is vrijgegeven:

Rosetta@home has been updated to version 5.62.

This version has the following features and updates:

1. there is now checkpointing for pose and jumping jobs
2. the percent complete has been fixed so that it will no longer go to zero after a restart if a checkpoint or model was made.
3. there are a few science related updates

[Kristof]

Slechts enkele dagen na de vorige update, is er een nieuwe.
Het changelog luidt als volgt:

Rosetta@home has been updated to version 5.64

There are a few new things:

1. This version has checkpointing for the fold_and_dock mode!

2. In the previous app (5.62), a change in the BOINC libraries caused a problem with older PowerPC Macs. This update should fix that problem.

3. We have added a new option to allow bigger moves during symmetric refinement of protein complexes.

4. We have also enhanced our ability to guide runs with information from previous runs by perturbing the energy function with a "barcode" (look for the word BARCODE to show up in some of your workunit names).

Er zijn ook nieuwe pictures klaar:

The Top Prediction images have been updated.Congratulations to Jaco J. Otto for predicting the lowest energy structure for the RNA 1esy!

[Kristof]

Nog een vermelding op de frontpage van Rosetta:

We forgot to mention that version 5.64 also includes 64bit applications for windows and linux platforms. These rosetta applications are copies of the 32bit version.

[Kristof]

Zoals hij beloofd had, een extra nieuws bulletin van David Baker:

Welcome to all of our new participants! The recent increase in computing power is very exciting and we are making good use of it!

We had a long meeting today with the three other research groups in Seattle we are collaborating with to create DNA cutting enzymes to correct mutations which cause diseases as I described a week or two ago. Our collaborators have tested a DNA cutting enzyme we have designed that targets mutations responsible for severe combined immunodeficiency disorder (SCID) in human cells and the preliminary results are that it targets the SCID site just as we designed it to! the next steps our collaborators will take with this and other disease targeting enzymes we are designing is to deliver them along with the normal (non disease) version of the gene into mice with the disease and see if the mutations are corrected and the disease cured. my students and I are impatient to see if we can cure human diseases with designed DNA cutting enzymes but our collaborators are emphasizing that a lot of testing has to come first.

I promised an explanaation of my "Search_Pairings" work units. as many of you know, many proteins contain beta strands which pair to form beta sheets. for many proteins, the key to predicting the structure correctly is getting the correct pairing between a critical pair of strands. the problem is that
in some cases the critical pairing forms extremely rarely. in the Search_Pairings work units I solve this problem by making a list of all possible pairings, and at the beginning of each of your calculationsn one of these pairings is randomly selected and forced to be present throughout the calculation of that structure. this procedure ensures that all pairings are sampled at a reasonable frequency so no critical pairings are missed. if you get one of these work units, see if you can pick out the pairing that is being kept fixed!

I am testing this approach out on proteins of known structure. In parallel, graduate student Rob Vernon is using the same approach to build models for the fibers formed by the alpa-synucein protein which are implicated in Parkinson's disease.

[Kristof]

Dit weekend wist David Baker ons nogmaals wat nieuws mee te delen:

A warm welcome again to all new rosetta@home participants. I hope you find participating in the project interesting and fun! We greatly appreciate your contributions!

As I have described previously, we are actively working on designing HIV vaccines that mimic different portions of the viral coat protein. This is a big effort with seven graduate students and postdoctoral fellows here at the UW working full time with Rosetta to design vaccine candidates, and many collaborating groups in Seattle, the NIH, and elsewhere testing to see if the potential vaccines elicit a neutralizing response to the virus. These very large scale projects are funded by the Gates foundation and the International Aids Vaccine Initiative. I will of course keep all of you posted on advances on this important problem! I should also emphasize that the computational design techniques we are developing for HIV should be applicable to other viruses, and we are thinking about starting up a project on Influenza within the next year.

I haven't described previously a complementary approach in which we design proteins not to mimic the virus, but to bind tightly to and inactivate the virus. We just completed the computational design of the first such protein, and have just started up the experimental testing. Our next step in this project is to design inhibitors that bind to and inactivate other human pathogens, we are currently deciding on the next target to go after.

[Kristof]

Rosetta@home has been updated to version 5.67.

1. This version allows us to specify extra information (from experiments) for which parts of an RNA should be buried and which parts should be exposed.

2. This version also allows the simulation of very large symmetric systems (like viruses) by actually modeling only a subsystem and inferring the energy and fold of the whole system.

[Mobster]

Zo maar even een complimentje tussendoor voor de PV-er van R@h. Knap hoe je dit elke keer bijhoudt. En post. Mijn complimenten dus

[bigbakkus]

Het is gewoon een dag taak ! Sjappo !

[Kristof]

een nieuwe client

Rosetta@home has been updated to version 5.68. This version allows us to carry out all-atom refinement for really large symmetric proteins where we simulate only subsystems, fixes a small bug in the RNA mode, and will allow a new sort of RNA simulation with lots of imposed base pairs.

[Kristof]

Rhiju kondigde een nieuwe versie van de client aan:

Rosetta@home has been updated to version 5.70. This version has some bug fixes for the RNA ab initio folding and symmetric folding and docking mode. We've also tried to fix some of the jumping around of the rmsd trajectory (the right hand rectangle), though the scaling still isn't perfect. Finally, we are also able now to model protein complexes with a different kind of symmetry than before.

Another interesting change: we are now able to send out workunits with the older application (5.68) and the newer one (5.70). This is advantageous because the older one is "stable" and lets us carry out long-term experiments such as looking for very rare low energy conformations with hundreds of thousands of workunits over several months. The new one has bug fixes for some modes as well as new features. The new one will be called "rosetta_beta_5.70" -- you can check out this link to see what's crunching.

[Kristof]

A lot of things have happened since I last posted!

For example, with your help, we now have a number of brand new designed enzymes that speed up the chemical reactions they were designed to catalyze by more than 50000 fold! This is a particularly exciting time because with the feedback from the experimental characterization of the designs computed with rosetta we are learning more and more about how to design new enzymes, and with this new knowledge we are constantly improving over our previous best designs. For example, for one of the reactions, the enzymes we had generated up until recently only worked once and then stopped working, but new designs we tested in the last couple of days just keep going. This is definitely a property we want to have in the enzymes we are hoping to design for carbon dioxide fixation and renewable fuel applications.

aldus David Baker in zijn Journal

[Kristof]

Nog een aanvulling van David:

I am just putting the final touches on four manuscripts that feature the work that all of you have done (and acknowledge participants who made key contributions) that have been accepted for publication; we will put pdf's of these papers and the others which have involved contributions from rosetta@home participants on the home page soon.

Ian Davis will be training high school teachers on how to use the first version of the "Rosetta Game" in the classroom in two weeks. We have come up with a really simple version that should be easy and hopefully fun to play that focusses on packing sidechains like puzzle pieces in protein cores. I am hoping to make it available to all of you in not too long so you can see what we are up to (and play the game yourself!).

[Kristof]

Een nieuwe client:

Rosetta@home has been updated to 5.72; some older workunits will continue to crunch with 5.68 (see previous post). What's new?

This version has a correction to one of the energy terms of the rosetta energy function which could improve discrimination of native structures.
This version fixes a small bug that was slowing down the 'relax' portion of work units.
The version incorporates several new features to the RNA mode that should greatly reduce file transfer for those workunits.
We will also be testing a new high-resolution energy function for RNA!

[Kristof]

Vandaag viel er iets speciaals op de frontpage van Rosetta te lezen:

Predictor of the day: Congratulations to Mechaniker (Team Dutch Power Cows) for predicting the lowest energy structure for workunit CNTRL_01ABRELAX_SAVE_ALL_OUT_-1iibA-_filters_1737_0 !

[Lord_Nemesis]

Gefeli Mechaniker

[Kristof]

Nog wat extra nieuws:
Zoals je gisteren in de DPCH kon lezen, werd het project enkele uren uit de lucht gehaald om een nieuwe fileserver op te trekken. Hier zijn enkele details:

We moved the backend of the BOINC system from our older fileserver (a dual 2.8 GHz Xeon w/ 2 GB RAM, running a 64-bit kernel and serving up 655 GB RAID5 disk (6 X 146 GB 10K SCSI)) to our fiber SAN. The SAN is a clustered filserver, running Polyserve's Matrix Server and serving up 16 450 GB SATA disks as a single RAID5 LUN via two Dell 2950s from within our group's fiber SAN. I'll post more information on and pictures of the SAN setup in the near future....

Daarnaast is er ook een nieuwe client uitgegeven:

Rosetta@home has been updated to 5.73; as with the previous update, some older workunits will continue to crunch with 5.68.

This version fixes a bug in high resolution modeling of RNA, and will let us test a more efficient procedure for closing "chainbreaks" introduced in certain workunits.

[Jejking]

En nog wat nieuws:

Ik heb Rosetta al eens draaiende gehad, maar met een paar weken heb ik m'n eigen computer, voor m'n studie een goedkope dualcore (journalistiek, video-editing ), en zodra ik die aangesloten heb op m'n kamer is het tijd om lekker mee te gaan rosetteren!

Net ingeschreven bij het team Dutch Power Cows, jullie allicht bekend Dan weten jullie dat.

[Pim.]

Welkom

[Kristof]

Nog een nieuw item in David Baker's journal:

I'm at the annual rosetta developers conference which started yesterday and goes through saturday. There are 90 developers from all over the world attending, and there has been a very exciting mix of new algorithmic developments and exciting applications to important biological and medical problems.

In a few weeks I will be describing our work on vaccine design at the upcoming HIV vaccine meeting in Seattle: http://www.hivvaccineenterprise.org/conference/program.html , maybe some of you will be there!

[Kristof]

The first game prototype is now online! we've put almost all of our efforts into a much more sophisticated version in which the game player collaborates with his/her computer and other players to solve difficult problems, but as an intro Ian Davis has put together a simple Java version that you can play without downloading anything on to your computer. we hope to build this into a fun way to explain the science we are doing on rosetta@home and as a warm up to the multiplayer human + computer version. Here is Ian's recent post, which you can also find on a thread he just started elsewhere on these pages:

Hi R@H community,

I've been working with several others in the lab on an "interactive Rosetta" project. The vision is that one day, you'll be able to interact with Rosetta as it runs, both (1) to help it produce better results and (2) to learn about what it's doing.

We're not there yet, but we have an early prototype for #2, the educational side. This is a simple "game" you can play in your web browser (using Java) to find the missing side chain for a designed protein that might be used to fight cancer. In this case, there's a small number of choices and the right answer should be obvious. However, it illustrates one of the basic steps that Rosetta performs thousands of times every time it designs a protein.

More "levels" for the game will be coming in the future. Also we're already planning to change the interface on the Java applet and to add a "score board" so you can compete against others, but if you try it out and have other comments or ideas to share, please post them here.

Here's the link: the Rotamer Game

[Kristof]

Een nieuwe client ...

Rosetta@home has been updated to version 5.77. The stable release has also been updated to 5.69. Both versions include a bug fix involving the scoring logic for closing chainbreaks.

... en nieuws van David Baker

The results of the last few days of computations of Rosetta@home on your computers have been pretty amazing! In collaboration with a group at the NIH, we experimented with adding a very small amount of information about protein structures from nuclear magnetic resonance experiments to the rosetta structure prediction process. this information is fairly easily obtainable, and doesn't seem like it would have much effect, but the results show quite contrary--the models produced are extremely accurate! this has the potential to revolutionize how scientists determine protein 3D structures using NMR data. We would never have been able to test the idea, which came up in a phone conversation several months ago, without all of your contributions.

Today I spoke at the AidsVaccine07 meeting about our work on designing vaccines. Scientists who have been working on this very challenging problem for many years are I think excited about our approach as it is something that hasn't been tried before and makes sense conceptually. While we are still far from a vaccine, our initial results with collaborators at the NIH are promising. I spoke to a reporter from the Wall Street Journal after my talk, and I think she is interested in writing an article on rosetta@home and HIV vaccine design.

[Kristof]

Een update in het journal van David:

Congratulations! Your collective results on structure prediction, protein structure refinement, and solving the X-ray crystallographic phase problem with rosetta@home were just yesterday accepted for publication as a research article in the journal Nature which many of you can find at your local newstands (I'll post here when the issue appears in print). As those of you familar with scientific publishing are certainly aware, Nature is probably the most widely read journal in the natural sciences, and only one or two research articles are published in any issue (almost all are shorter letters), so your work will reach a very broad audience and have exceptionally wide impact.

[Kristof]

En een nieuwe client:

Rosetta@home has been updated to version 5.78.
This version adjusts the way that experimental data is used to guide some RNA folding runs; there's also a new feature that lets us choose building blocks for RNA folding from different existing source structures.

Also, this version should improve folding efficiency in runs that involve a special type of symmetry (''D2'').

[Kristof]

Nu het project, na enkele dagen offline te zijn geweest, terug "up-and-running" is, zijn er enkele meldingen bijgekomen.
Eerst de algemene, die te vinden is op de homepage:

Sep 08, 2007
Rosetta@home has experienced a horrendous hardware/fireware failure. We essentially lost the SAN partition upon which the project was running! The newest edition of our SAN hardware was shipped with a firmware revision that contained an insidious bug - one which caused the new SAN disks to vanish after roughly 45 days of service. We - or rather I (KEL) - apologize for the inconveinence, lost time and lost effort that you have endured during our outage. We know full well that your contribution hinges on the understanding that we make maximum use of your valuable resources - that we not waste your time, CPU cylces or good humor. We are planning to express our disappointment to our vendors in clear terms, specifically siting the importance of this project to our research effort. We'll keep you abreast of the outcome.

Daarna nog een verklaring én wat nieuws van David Baker, himself:

As almost all of you know, we had the largest computer failure in the history of Rosetta@Home last Tuesday. Not only were we unable to make use of your valuable contributions, but also all of our internal computers were down as well, so the graduate students and postdoctoral fellows in my research group have had their resaearch projects stalled out. Quite a disaster! Fortunately, Keith and Chance, the computer gurus who keep Rosetta@Home and the group cmputer clusters running, are absolute pros, and they have worked miracles to get the project back on line even with this catastrophic failure. (to give you an idea, whenever anybody at the UW wants to set up a computer cluster or has any question to do with large scale computing hardware, Keith and Chance are the people they go to to find the answer). From Keith's most recent email, it appears that things are not fully back to normal, but hopefully we will be running as strong as ever very soon. In fact, as I will post once we are back up to speed, we have a very pressing scientific challenge we will need all of your help on!

Now for the good news!

As many of you will remember, you started seeing RNA molecules folding on your screensavers in addition to proteins about 9 months ago. Rhiju had generalized the Rosetta folding methodology beyond proteins to RNA which also adopts folded functional structures in addition to being a critical component in the reading of the genetic code inscribed in DNA. Using your computers, he tested his new RNA folding protocol, and the exciting results he obtained he reported in a paper that was submitted to the proceedings of the national academy of sciences (PNAS) several months ago. The paper was accepted with rave reviews, and has just appeared in print.

It is the policy of the PNAS journal to highlight for each issue the papers of exceptional interest. Your work, as reported in Rhiju's paper, is the major highlight of the issue of PNAS that just appeared! You can read about this months highlights in PNAS at

http://www.pnas.org/misc/highlights.shtml

In this paper, as in all of our papers (quite a few by now!) that have relied absolutely on your contributions, we have thanked all rosetta@home participants and cited by name those contributors who found the lowest energy structures. You can see the list at

http://www.pnas.org/cgi/data/0703836104/DC1/7


Thank you for your contributions, and we look forward to many more important scientific advances with your help at rosetta@home in the next year!

[Pyrus]

Blijf het mooi vinden dat er uit een DC project 'tastbare' wetenschap komt rollen Alhoewel andere projecten natuurlijk ook allerlei toffe dingen doen, vind ik het gewoon erg leuk dat er hierdoor daadwerkelijk papers verschijnen

[Kristof]

En een nieuwe client:

Sep 13, 2007
Rosetta@home is currently down due to a technical problem. We are working on a solution.
Sep 13, 2007
Problems solved! Rosetta@home has been updated to version 5.80. This version contains support for having small molecules present in protein-protein docking simulations. This is used in the current round of Capri. For details, see this thread.

[Megaflix]

Pyrus schreef op zondag 09 september 2007 @ 13:11:
Blijf het mooi vinden dat er uit een DC project 'tastbare' wetenschap komt rollen Alhoewel andere projecten natuurlijk ook allerlei toffe dingen doen, vind ik het gewoon erg leuk dat er hierdoor daadwerkelijk papers verschijnen

Ik denk dat dat bij die andere projecten ook wel zo zal zijn, dat er papers geschreven worden bedoel ik dan, maar die maken het misschien niet bekend.

Het leuke van R@H is juist de feedback die je krijgt op onderzoeksresultaten

[Kristof]

De problemen met de fileserver zorgen nog voor naweeën:

Sep 17, 2007
We're experiencing another hardware problem that is effecting the overall project, causing the validator and assimilators to fall behind. The temporary fileserver to which we've switched has dropped on of its RAID disks. We've found a replacement and the RAID is rebuilding now. Once finished the project should start catching up w/ itself...

[Mobster]

O jee. Dadelijk even de diverse bakjes maar even controleren dan. Zou spijtig zijn als ze stonden te idlen...

-edit-
Over die feedback vanuit het project. Vergeet ook het werk van onze PV-er niet hè. Ik ga echt niet elke dag alle projectpagina's af dus als er nieuws is moet het ook nog hier gepost worden en daar hebben wij Kristof voor

[ Voor 52% gewijzigd door Mobster op 18-09-2007 15:30 ]

[Kristof]

Na een tijdje stilte van David, is er een nieuwe update verschenen:

We have made huge progress with the interactive video game version of rosetta. We are on our sixth trial so far, with many improvements being made at each step. in the most recent trials, a subset of the people who have tried have become hooked and played (competitively) for many hours in a row. our goal now is to increase the fraction of people who get really into the game by adding animations and other information at the beginning to help guide people starting to play for the first time.
Within the next month I will be asking for volunteers for a more general trial. The reason for all of the trials is that we want to have the game really perfect before it goes fully public. Again, the two main goals are (1) educational--I'm convinced that people playing the game will gain a huge amount of insight into what biomolecules are and how they work and (2) research--we think people playing the game may be able to find much lower energy structures than the computer working on its own. time will tell!
On the science side, we are just completing two manuscripts describing landmarks in molecular biology: the design of novel enzymes (using computational protein design and rosetta@home) that catalyze chemcial reactions for which there are no naturally ocurring catalysts. (perhaps one of the experts among you can explain what this means on the "discussion" thread). I presented this work at two recent scientific meetings and people were pretty blown away. This opens the door to creating new catalysts for all sorts of chemical reactions that are difficult currently or require toxic or environmentally unfriendly reaction conditions.

[Vold]

Dus we kunnen straks ook onze eigen hersenen gaan inzetten om extra puntjes binnen te halen? Ben benieuwd..

Rosetta blijft toch wel goed bezig kwa updates, toppie!

[Kristof]

een kleine update vanwege David Baker (wie anders )

There is a news article describing all of your work (plus a strange picture) at
http://www.nature.com/news/2007/071016/full/449765a.html. the print version should follow
in a week or so.

[Kristof]

Een kleine update van de engine:

Rosetta@home has been updated to 5.81.
This version adds a new feature that allows us to properly model disulfide bonds in proteins.
Due to some bookeeping issues, the current stable version of Rosetta 5.69 is now 5.82.

[Jejking]

Het enige waar ik op wacht is die ver*********** update met ondersteuning voor de ATi HD2xxx-reeks. Volgens mij zijn ze daar supersterk in. Maar helaas is er nog geen nieuws over.

Zowel niet voor Rosetta als voor Folding

[Kristof]

Rosetta@home has been updated to 5.85:

• New features include proper diagnostics for a different kind of symmetry ('D2')

• A fix to the modeling of large symmetric complexes, and a lower memory usage by some of those jobs as well.

• A new output format that may be useful for designing new proteins.

• Some major improvements in the energy function used in RNA structure prediction, which we look forward to testing on a large scale!

[Kristof]

Ook nog een nieuws update van David Baker:

We have been working hard on a new streamlined version of rosetta which will soon be running on rosetta@home. there are so many developers of rosetta that the code grew very large and somewhat disorganized, and several members of the rosetta develpment community took it upon themselves to write from scratch a modern completely object oriented version. many others have joined in more recently, and the new version is now almost up to speed. we can tackle some new problems with this new code, as well as all of the old ones, so we will be gradually transitioning over in the next six months.

among the new things to come in the relatively near future include virtual drug screening by large scale docking of small molecules onto protein targets. accurately docking even a single small molecue onto a protien target is fairly computationally intensive, so if we want to dock 100 or 1000 possible drug candidates onto a protein target large scale computing will definitely be critical.

[Kristof]

een update van David Baker i.v.m. de problemen van vorige week, alsook wat nieuws over het game dat ontwikkeld wordt:

I aplogize for the rosetta@home site being down mid last week. Fate was against us: just as David K. was going in for surgery on his arm, a problem arose with the job feeder; normally David would have caught this immediately but it took the rest of the team a couple of days to figure out what was happening and how to fix it. Thanks to Rhiju for fixing the problem in the end.

We have a very early and preliminary version of the rosetta game ready for testing and will soon be looking for volunteers. If one of you can collect email adresses of people interested in trying it out, I'll post instructions on who to send it to later this week. We don't want to make it completely public until all the bugs are out and it is truly fun to play!

[Jejking]

Kristof schreef op maandag 03 december 2007 @ 08:07:
een update van David Baker i.v.m. de problemen van vorige week, alsook wat nieuws over het game dat ontwikkeld wordt:

[...]

Cool idee van die game .

Waar zou dat over moeten gaan? Even zoeken

[ Voor 3% gewijzigd door Jejking op 03-12-2007 09:50 ]

[Mobster]

Krijg nou niks!

[Lord_Nemesis]

Gefeli!

[Kristof]

Een update van David i.v.m. het game dat momenteel in ontwikkeling is:

I'm delighted by the early reviews of the rosetta game, which you can sign up to play and test as organized by the terrific rosetta@home moderators at
http://boinc.bakerlab.org/rosetta/forum_thread.php?id=3789

We still have some polishing to do before the game goes public--we want it to be as good as possible by then! The current plan is to use a "viral" distribution model for the next several weeks in which people testing the game can invite friends to play as well, an advantage of this is that the friends can go to the person who invited them to get up to speed on how to play, strategies, etc.

en een update i.v.m. het huidge onderzoek dat bezig is:

You can now read about a very exciting collaborative research project we (and you) are involved in which aims to use computational protein design to repair mutations in genes which cause disease. This is a collaboration between basic science researchers and clinicians at Children's hospital and the Fred Hutchinson Cancer research center in Seattle who treat patients with these diseases. The url is:

http://research.seattlech...s/immunity_vaccines/ngec/

This is one of a small number of "Roadmap" projects recently funded by the NIH which apply cutting edge basic research to work towards novel cures for diseases.

[Jejking]

Er zijn trouwens toch geen plannen voor een GPGPU-cliënt toch? Dat is wel jammer, dit project en Folding@Home zijn m'n favoriete projecten, en voor Folding@Home kan het wel binnenkort met een HD2600Pro (tenminste, als we de forumluitjes daar moeten geloven).

[Kristof]

Rosetta has been updated to version 5.89. Changes allow us to model proteins with complex symmetries, and improvements in the energy function used to simulate RNA.

Version 5.89 includes:
the ability to model symmetric complexes with new kinds of symmetry (dihedral with several monomers, e.g., D5),
a fix for an occasional crash that occured for large symmetric complexes,
a new option for regular protein structure prediction that prevents large movements during the full atom refinement,
and improvements to the RNA energy function.

[ Voor 51% gewijzigd door Kristof op 21-12-2007 10:18 ]

[Kristof]

Rosetta@home has been updated to version 5.90. New stuff:

1. Better conformational space exploration of proteins with "dihedral" symmetry.

2. Reduced virtual memory requirements ... 5.89 which was causing problems on some machines.

3. Compiled with the newest BOINC API, which should allow new users that download upcoming versions of the BOINC client to run Rosetta properly.

[Kristof]

Rosetta has been updated to 5.93. This version includes an improved treatment of dihedral
symmetry of proteins. This is a common, biologically important symmetry found among protein homooligomers (a collection of proteins with the same sequence and often structure). Thanks for supporting rosetta@home!

[Kristof]

En een update met wat uitleg over de momenteel actieve workunits:

In the previous post Rhiju described a simulation called FOLD-AND_DOCK where we are predicting the structure of protein complexes from sequence alone. In a cell few proteins carry out their function on their own. Most proteins are either forming complexes with other proteins a fraction of the time (and the structure of these is something we try to predict with protein-protein docking simulations) or form permanent complexes consisting of multiple chains. Predicting the structure of a protein complex from sequence(s) of the involved chains is something that has never been shown, mostly because of the enormous search space that has to be covered in such a simulation.

A very important class of protein complexes are those that contains multiple copies of the same type of chain, we call them homooligomeric. A vast majority of these homooligomeric proteins contains some type of internal symmetry. For example, the most abundant form of homooligomers are dimers (two identical chains) and most are symmetrical: if you rotate one chain 180 degrees you get the other partner in the complex.

The fact that they are symmetrical allow us to reduce the search problem (all the chain are internally identical and are related by a set of rotations and translations specified by the type of symmetry). This makes it feasible to try to predict the structure of symmetrical protein complexes from sequence. Its still a huge search problem, and thats why we need your help!

Right now we are trying to predict the structure of a protein with pdb code 1zpy. The size of this protein is actually around 900 residues and if we succeed it would make the largest protein structure predicted to atomic accuracy from sequence (About 8 times larger than anything predicted before). We
are not actually simulating the whole protein, we can make use of symmetry to reduce the problem, but its still a large simulation. So if you get a job with the 1zpy in the name be patient!

Why are we doing this? Homooligomeric proteins are a biologically very important class of proteins. They are forming virus capsids, proteins that cleaves DNA, hemoglobin that transport oxygen, actin involved in muscle contraction, channels that transport ions and secretion systems used by pathogenic bacteria just to give a few examples.

[Jejking]

Kristof schreef op woensdag 09 januari 2008 @ 09:07:
Verhaal

Ik heb net die hele 1zpy-batterij gehad, dat was echt niet leuk meer. Net begon de client te mekkeren dat hij overwoog om me geen credits te geven omdat m'n pakketten al 5.5 dagen te laat waren. Gelukkig trek ik nu het laatste pakket erdoorheen, af in een uurtje of anderhalf.

We zitten nu bij Rosetta Beta 5.93 trouwens, T021

[Kristof]

Nog een update van David Baker:

A lot of progress has been made in the last month!!

Our efforts to design new enzymes have been very successful, and it is likely you will be able to read about this progress in magazines available at local news stands--I'll keep you posted on this.

The new version of Rosetta, with many new capabilities, now appears to be stably running on Ralph, and David Kim is going to set it up on Rosetta@home in the next day or two. While the science will be new, the graphics will be a bit primitive at first, so please bear with us! We will be testing out new approaches to protein structure prediction in preparation for CASP8 this summer.

The rosetta game continues to improve with new features and new challenges. Until we are satisfied that all the bugs are out, we will remain in a "viral" distribution mode; if you would like to play you can request an invite from one of the volunteers testing out the current version.

[Kristof]

Feb 05,2008
A new application called 'minirosetta' has been released. This application is a complete restructuring of the current rosetta applicaton and was designed to facilitate future development and science. Our goal is to gradually transition to this application as it matures. Graphics are not yet available but are currently under development. Please post any issues/bugs in this thread. We'll be issuing tasks in relatively small batches soon.

[Jejking]

Kristof schreef op woensdag 06 februari 2008 @ 13:24:
[...]

Wat moet ik me hierbij voorstellen? Een miniclient?

[JohanDM]

De ontwikkelaars van Bakerlab zijn de rosetta client van scratch aan het herschrijven in C++, omdat de huidige die in C geschreven is met Fortran roots, bijna niet meer te onderhouden is.
Deze nieuwe client noemen ze voorlopig 'minirosetta' omdat alle functionaliteit en strategieën voor berekenen van modellen uit de huidige rosetta applicatie nog niet geïmplementeerd zijn. Ze zijn dus bezig de client terug op te bouwen. Ze releasen minirosetta nu al om te zien hoe deze minimale herimplementatie zich gedraagt in een real life boinc scenario. Zo kunnen ze het nieuwe design valideren voor ze alles hierin gaan implementeren.

[Jejking]

Hier het bewijs dat Minirosetta released is: Jejking in "\[Rosetta@Home] hitparade van 7 februari"

[ Voor 7% gewijzigd door Jejking op 08-02-2008 21:30 ]

[Kristof]

These are exciting times!

first, please bear with us! the all new beautiful completely object oriented C++ rewrite version of Rosetta is now running on your computers. old timers will recall that in the early days of the project, it took sometime before all the kinks were worked out, and that the graphics took some time to get to the very nice state we have all become used to. the new version of rosetta is extremely powerful, but as it is very new, there are still some rare problems surfacing, and some of the bells and whistles, such as the screensaver, are not yet in place. similar issues have been slowing us down a bit with our in house research and computing projects. rest assured however, that these problems will be solved quite soon, and the new version is so much more powerful that this inconvenience will be made up for many fold.

second, the game continue to progress, and I think is getting more and more fun to play. still some things to work out, so not quite ready to go public, but I encourage any of you who are interested to give it a try (see thread below).

third, as I alluded to in my last post, we have two very exciting papers describing a major breakthrough--the computer based design of new enzymes catalyzing novel chemical reactions-- that will be appearing soon, for a preview you can look at the current online issue of Nature.

[Kristof]

Uit het journal van David Baker :

The most recent of the many scientific papers that have come out of all of your efforts at rosetta@home is in today's issue of Science magazine:

http://www.sciencemag.org/cgi/content/abstract/319/5868/1387

This paper describes the computational design of new catalysts for chemical reactions. Among the many applications are removal of toxic compounds in the environment (bioremediation), making much easier difficult steps in the synthesis of drug molecules, and the generation of new biofuels.

Thanks again for all of your help!