Folding@Home 2.0 - An Online Protein Folding Game

a boy named woo writes "Tired of justifying your gaming addiction? Now you can really help accomplish something while you play... thanks to Howard Hughes Medical Institute researcher David Baker at the University of Washington." In collaboration with others, Baker has designed a game, called "Foldit," with a practical outcome: players manipulate on-screen images of protein chains and attempt to predict their folding patterns. From the article: "'Our main goal was to make sure that anyone could do it, even if they didn't know what biochemistry or protein folding was,' says [co-creator Zoran] Popovic. At the moment, the game only uses proteins whose three-dimensional structures have been solved by researchers. But, says Popovic, 'soon we'll be introducing puzzles for which we don't know the solution.'"

A Simpsons quote comes to mind

[Anonymous Coward]

But, says Popovic, 'soon we'll be introducing puzzles for which we don't know the solution.'"

Yay, everyone's a winner!

>----Joke-----

[Eco-Mono]

I always figured protein folding was one of those "hard to do, easy to check" type of things. Then again IANAMB.

Re:----Joke-----

[Anonymous Coward]

You are not a miniature boxer?

Re:----Joke-----

[oever]

No, it's the other way around. There are many ways to fold it so folding is easy. But there is only one solution with the lowest (free) energy. The number of ways to fold is very large. To determine if your solution is the lowest, you have to check all possible ways of folding. So in this game, they'll let you fold and if you are better than all the human and computer opponents for a certain period, you probably get some points.

Re:

[Anonymous Coward]

But there is only one solution with the lowest (free) energy.

But therein lies the crux of it - not all biological molecules follow the lowest (free) energy model. They may have been forced into a specific fold by other proteins or stabilized by other means. Just assuming lowest (free) energy fold = right fold is not correct and unfortunately the only metric available for completely unknown folds.
If you look at known sequence patterns (motifs) then you can assume it will fold the same, try to fit it and compare the fold with other proteins with the same motifs whos

Re:

[nschubach]

But letting people "game" certain types of folds permits these folds the ability to be removed from further calculation, right? You would be making progress either way. Personally, I think it would be cool if you could disguise the folding in other games like FPS where shooting certain bots triggers a fold of a certain kind on you, the protein molecule. Make the calculation minute and let some gamer perform it as many times as they want checking to see if it works or not.

Re:

[rts008]

No, you don't get some points.
You get to stand between their clothes dryer and laundry basket for the next game, and show off your '1337' folding skills.

*ducks and runs- 'cause I Am Not A Miniature Boxer either*

Well, the idea is to find out the solution

[Moraelin]

Well, another quote comes to mind: "I shall not today attempt further to define the kinds of material [under discussion] . . . but I know it when I see it." -- Supreme Court Associate Justice Potter Stewart, after failing to define what counts as obscene.

In this case, it's the program which knows it when it sees it. If the atoms can stay in that configuration, it's a solution. It's not known in advance, but it can be known if you reached a solution anyway.

On a more pragmatic note, though, well, the problem is that a human dragging atoms around is massively _slow_ compared to a computer. A puzzle you could realistically complete in a couple of days (i.e., before Joe Average completely loses interest, for lack of any visible progress or achievement or reward), the computer runs through them in seconds or minutes.

So basically simple proteins that you can realistically visualize and toy with as a puzzle, have been solved already anyway. Even if you managed to find a simple one that we don't already know how it folds, Folding@Home would run through it in seconds or minutes.

The problem are the big and complex ones. And I'd _really_ like to see anyone folding a beast like Hexokinase [wikipedia.org] by hand.

Or to give you an analogy, think of the game Atomino. Now think Atomino with several thousand atoms. It's not as much a puzzle, it's something straight from Call Of Chtulhu. If you even managed to wrap your mind around it all, well, it'll probably stay bent ;)

Re:Well, the idea is to find out the solution

[mweather]

Folding@Home on my PS3 take a couple hours at least per nanosecond of folding. A work unit is not a fold. It's a tiny fraction of a fold which can take thousands of nanoseconds. If a human can solve it in a day, that's a VAST improvement.

Re:

[blair1q]

Your PS3 has a tiny fraction of the computing power of a current quad CPU and triple-SLI gaming cards. Throw in a dedicate physics-engine chip, and a decent gross-solution partitioning algorithm, and there's little that the computer can't do faster than you.

It's silly of these "researchers" not to put some real brainpower on that.

Re:

[LinuxGeek]

Not quite right [stanford.edu]. There is a big difference between PPD and actual work produced, scoring varies for cpu, ps3 and gpu results.

Re:

[Anonymous Coward]

Have you tried playing the game? You're pulling atoms around, but you also have the same toolbox that the computer has when it's trying to fold a protein, including gradient-based minimization, side-chain repacking, and cavity detection. The idea behind fold.it seems to be that humans might have better judgement about how to applies the tools used for protein structure prediction.

Also, Folding@Home takes an extremely long time to fold proteins of any reasonable size compared to a program like Fold.It. The s

Re:

[AndersOSU]

I tried playing, but got sick of the grind. I give it 2 weeks before someone comes out with a bot that does the work for you. The bot will ruin the balance, and no one will want to play anymore.

Re:Well, the idea is to find out the solution

[Opportunist]

The "game" has two options to automatically "shake and wiggle" a molecule for collisions and misalignments a computer can easily identify. You don't have to handle trivial collisions by hand.

But there are certain problems that are easy for a person because humans can visualize and imagine a structure, something a computer simply cannot. This is exactly what this program is about. You look at such a molecule and can easily determine that bending it here or there allows you to crunch it further. A computer would have to try all, or at least many, combinations that you already exclude as pointless just from looking at them.

Well, that's kinda the point

[Moraelin]

But there are certain problems that are easy for a person because humans can visualize and imagine a structure, something a computer simply cannot.

Humans can imagine and visualize _simple_ structures, yes. More complex stuff, well, I posted a link to a picture of Hexokinase. You try visualising and imagining that. If you can, well, you have a better imagination than I do :P

Re:

[Opportunist]

Funny enough, this picture is a bit like the ones you get shown at IQ tests (you know... "what does this look like unfolded").

Now, I don't have the ability to visualize this molecule immediately either. But like IQ tests can be trained, I'm sure that with some training you can.

Re:

[Anonymous Coward]

Or to give you an analogy, think of the game Atomino. Now think Atomino with several thousand atoms. It's not as much a puzzle, it's something straight from Call Of Chtulhu. If you even managed to wrap your mind around it all, well, it'll probably stay bent ;)

OK, that's it. I'm signing up now!

(Dude, seriously, if you're not on the project staff, you should be -- on Slashdot, that sort of comment is the best recruitment invite that could possibly be written.)

No Linux version and no source code

[oever]

All that's there is the windows executable [fold.it] and the mac executable [fold.it].

Re:No Linux version and no source code

[Anonymous Coward]

You mean it only supports >95% of computer users? What an outrage!

Re:

[mweather]

Or approximately 1% of the people geeky enough to try this.

Re:

[Danathar]

Have you tried it? It's INCREDIBLY addicting and just about as simple as Tetris to play. My mother picked it up in under 5 min and was playing for HOURS.

That's enough for me. It's going to be hit.

Re:No Linux version and no source code

[laddiebuck]

I'm one of the game creators; and there IS a linux version, I use it every day, but somehow the story broke a day too early. Just hang on, please.

Re:

[Anonymous Coward]

I just thought I'd warn you.... Jack Thompson is writing to your mum. He heard about an add-on that lets you shoot law-enforcement genes.

Re:

[1 a bee]

Do post back here, then, when the Linux version is ready, please...

Re:

[t35t0r]

is there way to change the settings so that I can go to the last level in offline play? Is there a registry setting?

Re:

[t35t0r]

figured it out just change "complete" to "1" in the .ir_puzzle files.

Re:

[t35t0r]

is there a way to convert the solution files to pdb files?

Re:

[SpeedBump0619]

How about a release for the iPhone? It would be so cool to be able to play with this during all thos 5-15 minute idle times I have. It seems like it would be a reasonable interface for it also.

Re:

[Anonymous Coward]

All that's there is the windows executable

And it required administrator privileges to install. Will anyone every learn to problem properly for Windows?

Re:

[ORBAT]

And it required administrator privileges to install. Will anyone every learn to problem properly for Windows?

Now that's a Freudian slip if I ever saw one.

Re:

[belmolis]

Just in case you're tempted, I tried it under Wine. The installer ran fine, but the game itself doesn't work.

Re:

[t35t0r]

It installs and plays fine under wine-0.9.60. I couldn't login because it said my account was still pending. My mom who is a crystallographer and builds proteins using more sophisticated versions of these programs played it for a few minutes and got really into it. The score is most probably based on a phi-psi torsion angle plot called a Ramachandran plot as well as other properties (e.g. hydrogen bonding, close contacts, hydrophobicity, etc). This is really ingenious.

Re:

[belmolis]

Interesting. My wine is 0.9.30. I guess 3d-level release numbers for wine are not just bugfixes.

Is it that hard to actually link to the game?

[Conspiracy_Of_Doves]

http://fold.it/ [fold.it]

Re:

[Profane MuthaFucka]

Oh darn you, you gave away the answer to the puzzle of the missing link. And I was SO CLOSE to solving it myself.

Re:

[p3d0]

"Darn you"? Not exactly living up to your name there.

Re:Is it that hard to actually link to the game?

[sootman]

Thanks. Eds, take note: please use that link in tomorrow's dupe. kthxbye

Then again

[TheShadow1276]

Who's to say that the wrong sort of mind will try to use this to make biological weapons of some sort? If it can be used to create beneficial wonders, it can be used to create terrible horrors.

Re:

[Gat0r30y]

Um, how precisely are you planning on folding proteins into evil ways? All you get here is a game where you fold em, your not doing much anything else. Puree of FUD.

Re:

[mweather]

Um, how precisely are you planning on folding proteins into evil ways?

Fold them into prions, then load them into artillery shells. 100% fatal, and no cure.

Re:

[Anonymous Coward]

+1 Funny? Or just another fucking idiot? It's so hard to tell these days...

Re:

[chartreuse]

Maybe brilliant. Something that refolded lots of proteins in your body would probably be lethal.

That's true about everything

[bigtrike]

Your argument is true about nearly every piece of science and technology ever created.

Re:

[account_deleted]

Comment removed based on user account deletion

Outsourcing bioinformatics!

[cynicsreport]

From TFA:

"My dream is that a 12-year-old in Indonesia will turn out to be a prodigy, and build a cure for HIV,"

We should give David Baker credit for bringing forced child labor into the 21st century! Think about it: thousands of children, solving protein stuctures for 12 hours a day, 7 days a week, at $0.50/hour. The prescription drug companies could lay off all their bioinformaticians, outsource their drug discovery program to Indonesia, and cure cancer in one fell swoop.

Sorry; oblig. Re:Outsourcing bioinformatics!

[NotBornYesterday]

thousands of children, solving protein stuctures for 12 hours a day, 7 days a week, at $0.50/hour

A Beowulf cluster of them?

Re:

[strider2k]

I can't even imagine a 12 year old working on that. Sure there are prodigies in math and science but protein folding is out of the chart. Education provided to a 12 year old usually does not include Advance Cellular Biology or Molecular Biology.

Re:

[zolf13]

... tempting idea ... now we know why they give away those XOs for free.

Re:

[Magada]

You just might be right - the next-generation workforce needs to be computer-literate (whatever that means), but there aren't enough kids to go around in the first world - the second and third will need to pick up some of the slack. That's how mass education started in the first place!

Re:

[Scott Francis[Mecham]

Actually, this reminds me of a short-story(can't remember if it was Gibson or Sterling) about drug-company employees using VR gear to test molecule interactions: the protagonist enjoyed the simulation so much that she refused to take a promotion(and played dumb on aptitude tests) so that she could keep "playing the game".

Re:

[rossdee]

Yougsters these days have it too easy, we used to have to work 29 hours a day, and pay mill owner for permission to come to work...

Re:

[DecoyMG]

Actually they are planning to give the program to middle school students, have to satisfy NSF's outreach activity requirements after all.

Re:

[Provocateur]

Think about it: thousands of children, solving protein stuctures for 12 hours a day, 7 days a week, at $0.50/hour. The prescription drug companies could lay off all their bioinformaticians, outsource their drug discovery program to Indonesia, and cure cancer in one fell swoop.

Damn, I could probably have my very own vat-grown ninja, thaw when needed, to get those kids off my lawn! After they've migrated here, of course.

Re:

[chartreuse]

I wish there was a +1 Sardonic mod.

Re:

[DerWulf]

I'd really quite like to know what your definition of "force" is ...

Better than Rubik's cube to test 3D skills

[moteyalpha]

Could be the next test of the true talent of a programmer. These have to be the most complex 3D problems ever. If a person were good at it , would probably be a paying occupation.

Re:

[tucuxi]

Not to mention that there are simple combinations of moves that will guarantee that the cube will get solved. You can cram those in before an interview and voila! an expert 3D problem solver.

A better test for a programmer would be to say "write me a program that solves rubik's cube"... or if you want to test for 3D prowess, ... graphically.

look mom, no more cancer

[2TecTom]

how about a quake mod?

Here's the game URL

[Trucid]

Seems like the editors aren't doing their job. http://fold.it/ [fold.it]

Baker heads up Rosetta

[Krishnoid]

Baker already heads up Rosetta@Home [bakerlab.org] , a BOINC [berkeley.edu] project that has your computer fold proteins in its spare time. He's appreciated for keeping his journal up-to-date and being responsive to participants; Folding@Home [stanford.edu] is somewhat less responsive (and doesn't provide the BOINC option).

Re:

[Digi-John]

I run Folding@home *because* it doesn't use BOINC. BOINC sucks really really bad

Folding@home, BOINC, FUD

[Anonymous Coward]

BOINC sucks really really bad

Troll much?

Seriously: I know that's a bit subjective, but I (and literally millions of others) disagree with that. I run BOINC on my computers because it does *not* suck. I run several projects on each, ensuring that when/if one has a server outage or workunit lull, my BOINC clients are doing something useful for someone *else*.

Perhaps you've never heard of or used the account managers BAM or GridRepublic; they make managing projects and client computers a breeze. They're easy to use but quite flexible.

I w

Re:

[Anonymous Coward]

Reason the account manager functionality wasn't baked into the server-side part of the platform is because David A. wanted to stress the BOINC stack as a technology anybody could use for a distributed computing platform. Basically anybody can throw a project together to solve whatever problem they want to solve, without having to clear it with David A. or myself.

Whoever runs an account manager has to make a judgment call about which projects they are going to expose, and by virtue of exposing it, they are s

Drugs get Copyrights ya?

[IronMagnus]

From TFA: "Baker has high hopes that the game will speed up the sometimes tedious business of structure prediction. But the part of the game that excites him most is scheduled to debut this fall, when gamers will be able to design all-new proteins. Novel proteins could find use in any number of applications, from pharmaceuticals to industrial chemicals, to pollution clean up. With the ability for any person with a computer and an internet hookup to start building proteins, Baker thinks the pace of discovery could skyrocket. âoeMy dream is that a 12-year-old in Indonesia will turn out to be a prodigy, and build a cure for HIV,â he says." ...But will that 12 year old get to own the copyright and sell it to the drug company and make billions? Or will the drug companies just steal it and keep the money for themselves...

Re:

[laddiebuck]

This is academia, not industry. We are publicly-funded. Most researchers do not make any money off their discoveries and just get paid from grants. So the poor Indonesian kid probably cannot expect to get rich quick, but at least can be accorded his due share of fame and the benefits arising from that.

Re:Drugs get Copyrights ya?

[Weezul]

Well if the company is smart they'd give him a job or scholarship or such. Anyway afaik drug companies never find proteins, they always "steal" them, i.e. patent the work of government paid university researchers, or buy the patents from the university for peanuts. All the drug companies actually do is the FDA "paperwork", which is actually quite costly, and the marketing.

In an ideal world, if the fed. gov. paid for the universities to do the research, they could also pay for the universities to get the drug some preliminary FDA approval. After that, any U.S. based (generic) drug company could produce the drug (completing their part of the approval process). However, only U.S. based companies would have this right.

Unprecedented

[Bovius]

This is the first time I've seen a project that combined distributed computation, using human minds for intelligence and processing power, and connecting the two with an interface that is intended to be entertaining and pleasant. I'm eager to see if they get any good results. If this is successful, it may set a precedent for using large numbers of people to crunch the kind of problems that computers find prohibitively difficult.

Wait a sec...distributed computation, human minds, pleasant interface...starting to sound like teh Matrix.

Re:

[Gat0r30y]

teh Matrix.

The marketing guys told us the matrix sounded scary and suspiciously close to something people heard in math class. It has been renamed the cloud - fluffy, pretty, sometimes looking like ducks or the virgin mary - for the public benifit.

Re:

[goombah99]

Part of the project actually is to determine what can make the game more fun. For me the funnest part is competing against others.

Re:

[raydulany]

Or The Diamond Age [wikipedia.org].

Re:

[Duncan3]

Been happening for a long time, this is just the first one with proteins :) Still cool tho.

Re:

[Bovius]

Any examples that you know of?

Torrent here:

[Anonymous Coward]

http://www.mininova.org/tor/1392891 [mininova.org]

Does not have a Linux client ...

[jopet]

Not usable for me.

Re:

[kel]

Not usable for me.

The developers will have one ready in a week or so....

Re:

[jopet]

Thats good news -- thanks.

Obligatory...

[uniquename72]

The adenosine triphosphate is a lie!

Re:Obligatory... (2)

[chartreuse]

Adenosine triphosphate is people!

download is about 50mb

[the brown guy]

A better game that is sort of similar involves folding eggs around cars, and the protein damages the paint!

Re:

[game kid]

I remember that game! Grand Theft Amino was a hit, but became rather infamous with the "Hot 11-S-storage" mod.

this could be the next big thing

[rritterson]

I work in a protein engineering/structure lab that has strong connections to the Baker lab, both in people and in scientific collaboration. The biggest project to come out the Baker lab is a protein structural modeling, simulation and prediction suite known as ROSETTA. While I'll gloss over some of the nitty-gritty about the methodology, suffice it to say that ROSETTA, through a combination of knowledge based and physics based modeling, has knocked the pants off of just about every other program out there used to simulate, design, and fold proteins. (Quantum-based physics models can be much better than ROSETTA, at the expense of a few extra superclusters and months of simulation time).

I no longer work as a ROSETTA developer or the "protein folding problem", but many of my lab mates do. They struggle with ROSETTA sometimes, as it comes close to predicting the real structure of a protein, and then falls away and wanders into another structure far from reality. If only it could 'see' the best structure when it came close!

The problem can be analogized with surveying a landscape. Imagine every square feet of dirt you can see is one possible protein structure, and you want to find the lowest elevation square foot. For a human, the visual search process is fairly quick and rapid. You can see a few hills out in the distance, but a much lower valley on the other side, where the land is lowest. It takes only a few seconds. On the other hand,a computer with no prior knowledge of the landscape can take a very long time to find that global minimum. The computer essentially has to drop a ball on the landscape and watch where it rolls, then pick it up, put it somewhere else and watch again (Physics and computer modelers forgive me!). It may never pick the right starting point to get over that far away hill.

Perhaps the brain can be as good at finding great protein structures as we are at finding lowest elevation points. Perhaps intuition about how a protein 'should' look can get us places a computer program never can without a ton of time and power. That's what this game is all about. The baker lab has done a fantastic job of turning a very hard scientific problem into a competitive game that is simultaneously fun, provides possible scientific information, and represents something of a human experiment on how our brains work.

This could be the next leap forward if it turns out some people have an innate knack for folding. It should be interesting to watch.

Re:

[TuringTest]

Do you have some general reference about this use of momentum in local search? I haven't encountered any research on this concept, and I'd like to know how the metaphor applies. Thanks!

Umm, this is rosetta@home, not folding@home

[bulletman]

This game is an offshoot of the rosetta@home [bakerlab.org] effort to model protein folding. Folding@home [stanford.edu] is a separate effort.

It's fun!

[QuantumG]

Yeah, I've been playing it.. it's pretty awesome. I have no idea what I'm doing but my score goes up.

As such, I'm pretty sure genetic algorithms could give similar performance.

Re:

[laddiebuck]

Forgive me, but the whole point is to outdo the computer. Rosetta, the current best algorithm and program (and screensaver) to do protein structure prediction already has sophisticated AI techniques (although the whole problem is essentially a hill-climbing problem), and the whole point is that we want to utilise the most sophisticated visual intelligence known -- humans -- to solve an essentially visual problem. Already very early in the trials, we saw humans, non-biochemists, beat Rosetta, and that patter

Re:

[QuantumG]

Oh I'm not. I'm just saying that the level of play that *I* am capable of is so low that I bet even the simplest algorithm could beat me.

Re:

[Anonymous Coward]

That's not really true. People have tried genetic algorithms for protein structure prediction, and it's actually non-trivial. The problem is that recombining different parts of proteins is difficult, because the parts that you're trying to combine together aren't compatible. The difficulty of recombining different structures leads to genetic algorithm not performing much better than simulated annealing, an algorithm which Rosetta actually uses.

OMG. This is INSIDEOUS. (I've just played it)

[Danathar]

Sheer genius. I don't normally get into puzzle games but this one had me playing for 45 min straight before forcing myself to stop. It's well designed and fun to play.

With tetris it was time wasted down the tubes. At least with this you are doing something useful (and it might save somebody's life).

I can just see this thing going to cell phones, PDA's, etc.

Re:

[QuantumG]

It crashed, that's why I stopped :)

froze on game 4 when I played it

[Optical Voodoo Man]

It froze on the loading of game 4 for me. Sucked up 100% of the CPU and wouldn't respond. Seemed slow before that point too. Might be an OK puzzle game but only if they get it working.

Then there's johnny

[ruiner13]

Johnny discovered the cure for cancer when he was 13. He had the inspired notion to try to fold everything into the shape of a phallus. This, it seems, was the key all along.

National Geographic
March, 2012

QuantumThermoDynamics@home

[raftpeople]

In this project users will map variables onto ingredients of typical recipes. After combining and cooking, the flavor of the resulting dish will determine which equations can be solved.

The Protein Gambler

[ppanon]

You got to know how to hold em, know when to fold em,
Know your alpha helix and beta sheets.
You never count your units when you're sittin' at the keyboard,
There'll be time enough for countin' when the protein's done.

Nintendo wii!

[LiENUS]

They should port this to the wii, Cant you just imagine it? 4 players competing to fold proteins

Re:

[corychristison]

I dunno.

Mario Kart Online is pretty hard to beat. .. damn that game is fun.

Re:

[LiENUS]

But when was the last time mario kart cured cancer?

Do I read this correctly ?

[aepervius]

"Currently, the username is rp and the database server is db1."

Is it that usual to give username and password of database over the net ?

pfft

[BorgCopyeditor]

I'm holding out for FoldingFolding@Home Revolution.

Link to movie of gameplay and UW news release

[kendor]

There is an FLV movie showing the gameplay as well as the University of Washington's news release on the topic at the UW's news site. Link to the news release and contact for media here:

http://uwnews.org/article.asp?articleID=41558 [uwnews.org]

wow

[DerWulf]

As others have said: this is fascinating. It makes sense too: Games are practical problem solving wrapped in eye candy and sometimes a story. Why not solve a useful problem why you are at it? The distributed wetware aspect is very cool as well.

I wonder: did you consider implementing the client in java? Will we see this game on cell phones or PDAs?