

Gamers solve molecular puzzle - sew
http://cosmiclog.msnbc.msn.com/_news/2011/09/16/7802623-gamers-solve-molecular-puzzle-that-baffled-scientists

======
schlomie
Explanation of the problem: <http://fold.it/portal/info/science#whygame>

Protein structure prediction: As described above, knowing the structure of a
protein is key to understanding how it works and to targeting it with drugs. A
small proteins can consist of 100 amino acids, while some human proteins can
be huge (1000 amino acids). The number of different ways even a small protein
can fold is astronomical because there are so many degrees of freedom.
Figuring out which of the many, many possible structures is the best one is
regarded as one of the hardest problems in biology today and current methods
take a lot of money and time, even for computers. Foldit attempts to predict
the structure of a protein by taking advantage of humans' puzzle-solving
intuitions and having people play competitively to fold the best proteins.

...

What shape will a protein fold into? Even though proteins are just a long
chain of amino acids, they don't like to stay stretched out in a straight
line. The protein folds up to make a compact blob, but as it does, it keeps
some amino acids near the center of the blob, and others outside; and it keeps
some pairs of amino acids close together and others far apart. Every kind of
protein folds up into a very specific shape -- the same shape every time. Most
proteins do this all by themselves, although some need extra help to fold into
the right shape. The unique shape of a particular protein is the most stable
state it can adopt. Picture a ball at the top of a hill -- the ball will
always roll down to the bottom. If you try to put the ball back on top it will
still roll down to the bottom of the hill because that is where it is most
stable.

~~~
InclinedPlane
Protein folding is quite possibly an NP-complete problem. Determining the
relative energy of a given protein-chain conformation can be done in
polynomial time, it's a pretty simple problem. However, minimizing the energy
is very difficult because there are so many degrees of freedom (on the order
of the number of amino-acids in the protein).

~~~
asdkl234890
Yet proteins fold in polynomial time in all living things.

~~~
timr
That's meaningless. They're not folding on a Turing machine, so "polynomial
time" isn't defined.

~~~
shiven
Quite right! However, all we have are (imperfect?) versions of a Turing
machine to solve the folding problem!

Maybe a Lisp machine would do better ;-)

At the end of the day, a linear sequence of amino acids has to end up in a
three-dimensional conformation with short-range contacts being formed between
atoms far away in the _primary_ (linear) sequence. Add to this the complexity
from long-range effects critical for the final structural stability and
biological/biochemical function.

And don't even get me started on Intrinsically Disordered Proteins -- where,
frankly, the future of the entire field lies !!!

~~~
jbri
Assuming this is an NP problem, then a nondeterministic turing machine is
capable of solving it in polynomial time (by definition).

So it stands to reason that a properly-constructed quantum computer (being an
approximation of a nondeterministic turing machine) would probably be able to
solve the protein folding problem in polynomial time.

It's also not out of the bounds of possibility for similar quantum effects to
explain how proteins fold the same way every time - an individual protein in
fact being a superposition of all possible foldings, and the lowest-energy
folding being the one that is actually observed whenever it interacts with
anything.

~~~
sid0
There is no known way of getting a quantum computer to solve an NP-complete
problem in polynomial time. Integer factoring is in NP but not complete for
it.

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irollboozers
I worked in the Baker Lab, which developed the game, with the UW iGEM team. We
actually used Foldit to make point mutations in a decapsulating protein in
Anthrax.

<http://2010.igem.org/Team:Washington>

I wasn't too aware of the large community of Foldit players at the time, but
it was really cool to see the lab bring in some of the top ranked players into
the lab to get their opinion on specific folding problems. A friend of mine
wanted to find the best design for a novel enzyme, and they actually brought
in a guy as a consult.

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shiven
Excellent! As a structural biologist, I found the coolest part of the entire
approach to be the use of energetically favorable FoldIt model as a staring
point for "molecular replacement".

I guess, this story highlights quite elegantly the "protein folding problem"
to be a canonical "P vs NP" problem! Exciting times!!

~~~
kayhi
I've had some success using the Zhang server (I-TASSER) to generate a model
for MR. The benefit ended up being finding a domain, which we hadn't known
based on our amino acid sequence. Exciting times indeed.

~~~
shiven
This seems to be in the same vein, kayhi :

[http://www.slideshare.net/ijstokes/wide-search-molecular-
rep...](http://www.slideshare.net/ijstokes/wide-search-molecular-replacement-
and-the-nebiogrid-portal-interface)

Will be used for my next project!

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Haraldson
I don't know much about molecular structures, but it's a really interesting
subject. The crowdsourcing aspect of this is also something that makes me
believe a little more in human kind.

Of course, if some idealistic _crowd_ were to find the cure for AIDS or a HIV
vaccine, some big corporation would surely claim the patents on it or
something; it is of course highly ethical to earn big bucks on others' misery,
instead of just getting the cure out there to the masses.

This story reminds me of the pilot of Stargate Universe, by the way. The
gamers will get to go to space now, right..?

~~~
earl
To be fair:

(1) Finding the molecular conformation is only a tiny piece of the puzzle.

(2) If we were to discover a vaccine for HIV, many countries such as India,
Thailand, Brazil, and China would instantly break any necessary patents. This
is at it should be -- the countries that can afford it fund R&D and those that
can't share in the results.

~~~
archangel_one
Something along the lines of a smaller version of (2) happened some years back
in South Africa, since they've got a higher rate of HIV than any other
country. IIRC, they were ignoring patents and manufacturing various medicines
locally instead.

Token citation: <http://en.wikipedia.org/wiki/HIV/AIDS_in_South_Africa#2001>

~~~
Haraldson
Yeah, good to know. These countries are probably too big even for big drug
corps to take on.

Do you know anything about the quality of the locally manufactured drugs you
mentioned, by the way?

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tintin
FoldIt = game (<http://fold.it>)

Folding@home = distributed computing (<http://folding.stanford.edu/>)

Both "to understand protein folding".

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yters
Sweet, but it's strange a slow human brain can solve this even when we have
super computers and the like working on the problem for many years. What's so
special about our brains?

~~~
stryker
It's not so surprising if you consider that humans are much better at pattern
recognition in general, where the space of possibilities is too large for a
brute force search (even with clever optimizations, such as minimax, alpha-
beta pruning, and hard-coded openings/endings).

Here is a specific example:
<http://en.wikipedia.org/wiki/Go_(game)#Computers_and_Go>

They've made a bit of progress with Go, putting in heuristics and strategies
specific to Go. But it basically amounts to translating human intelligence
into code, or what researchers refer to as "domain knowledge".

Surely, machines are orders of magnitude faster than humans, for certain
things. Just not all.

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mhb
How come they're not offering large cash prizes for solving these in order to
encourage more participation?

~~~
td
Because up until now, it's working just fine without large cash prizes, I
guess.

~~~
mhb
I suppose that depends on your sense of urgency.

~~~
eavc
Are cash prizes all that helpful in fostering insight?

I recall a demonstration at TED where cash incentives cause a worse
performance, maybe due to pressure.

So if people are showing up on intrinsic motivation alone, it might be good to
let that lie.

~~~
mhb
They seem to have worked pretty well for Netflix and the X prizes.

