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Proteins Made To Order

samzenpus posted about a year and a half ago | from the molecules-to-go dept.

Biotech 51

ananyo writes "Proteins are an enormous molecular achievement: chains of amino acids that fold spontaneously into a precise conformation, time after time, optimized by evolution for their particular function. Yet given the exponential number of contortions possible for any chain of amino acids, dictating a sequence that will fold into a predictable structure has been a daunting task. Now researchers report that they can do just that. By following a set of rules described in a paper published in Nature (abstract), a husband and wife team from David Baker's laboratory at the University of Washington in Seattle has designed five proteins from scratch that fold reliably into predicted conformations. The work could eventually allow scientists to custom design proteins with specific functions."

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51 comments

So what? (-1)

Anonymous Coward | about a year and a half ago | (#41929807)

Can't you already order proteins at McDonalds?

I have my order in.. (1)

mrbluze (1034940) | about a year and a half ago | (#41929843)

I want them to synthesize a fully functioning Marylin Monroe to go with my 3D printed vintage sports car.

Honey, let's make proteins tonight (3, Funny)

cyberdime (2750427) | about a year and a half ago | (#41929929)

By following a set of rules described in a paper published in Nature (abstract), a husband and wife team from David Baker's laboratory at the University of Washington in Seattle has designed five proteins from scratch that fold reliably into predicted conformations.

Barring certain genetic anomalies, it should be pretty easy for any husband and wife team to produce protein sequences that result in predicted conformations.

Re:Honey, let's make proteins tonight (0)

Anonymous Coward | about a year and a half ago | (#41931333)

That's a really fucked-up idea.

Re:Honey, let's make proteins tonight (1)

nitehawk214 (222219) | about a year and a half ago | (#41931821)

I want them to synthesize a fully functioning Marylin Monroe to go with my 3D printed vintage sports car.

Barring certain genetic anomalies, it should be pretty easy for any husband and wife team to produce protein sequences that result in predicted conformations.

Sex can produce cars?

Re:I have my order in.. (1)

eastlight_jim (1070084) | about a year and a half ago | (#41930885)

I love the juxtaposition of your comment and your sig.

God says... (-1)

Anonymous Coward | about a year and a half ago | (#41929861)

32:32 Therefore the children of Israel eat not of the sinew which
shrank, which is upon the hollow of the thigh, unto this day: because
he touched the hollow of Jacob's thigh in the sinew that shrank.

33:1 And Jacob lifted up his eyes, and looked, and, behold, Esau came,
and with him four hundred men. And he divided the children unto Leah,
and unto Rachel, and unto the two handmaids.

33:2 And he put the handmaids and their children foremost, and Leah
and her children after, and Rachel and Joseph hindermost.

33:3 And he passed over before them, and bowed himself to the ground
seven times, until he came near to his brother.

33:4 And Esau ran to meet him, and embraced him, and fell on his neck,
and kissed him: and they wept.

Re:God says... (0)

foniksonik (573572) | about a year and a half ago | (#41931165)

WTF?

And it continues (0)

Anonymous Coward | about a year and a half ago | (#41929893)

Our efforts to understand how matter becomes life! We will understand it, and we will be able to extend life as a result.

Competitive advantage (4, Funny)

srussia (884021) | about a year and a half ago | (#41929951)

FTFA: "The work was spearheaded by husband-and-wife team Nobuyasu Koga and Rie Tatsumi-Koga"

A centuries-old tradition of origami!

Re:Competitive advantage (1)

drinkypoo (153816) | about a year and a half ago | (#41932181)

A centuries-old tradition of origami!

Not to mention the long and hallowed tradition of husband-and-wife teams engaging in protein-folding experiments...

Evolution does it again.... (-1)

Anonymous Coward | about a year and a half ago | (#41929997)

And it is so well personified in this Slashdot story of how these "enormous molecular achievements" which can have an "exponential number of contortions" evolved themselves into the building blocks all organic life forms. Now we're invited to celebrate the achievement/intelligence of these ones who managed to fold a simple protein that would have folded itself into something far complex and useful, given enough time to "evolve"? Am I the only one who sees the vanity in this reasoning? Why is it so amazing when the intelligence of man achieves something which for those who believe in evolution, is so insignificant in the grand scheme of things? How about we stay quiet until we can create a living thing from scratch that's more impressive than the life-forms the random unintelligent process of evolution has come up with. And if/when you do, know that you would have most likely just reproduced all that you learned from existing life on earth and that would be cheating.

Re:Evolution does it again.... (4, Interesting)

ColdWetDog (752185) | about a year and a half ago | (#41930065)

Because, unless your're His Noodliness, you have to start out small. We can make DNA of reasonable length but we don't know how to create a sequence that will cause a protein to fold in a specific pattern to it will have a specific function and not act like a disorganized blob of glop.

You want to be the whole spaghetti, not just the stuff tossed out in the sink.

Re:Evolution does it again.... (2)

ArcadeMan (2766669) | about a year and a half ago | (#41931363)

You should be careful about the lies you spread around. One of these days, the great Invisible Pink Unicorn will get you.

Re:Evolution does it again.... (1)

gomiam (587421) | about a year and a half ago | (#41930085)

Now we're invited to celebrate the achievement/intelligence of these ones who managed to fold a simple protein that would have folded itself into something far complex and useful, given enough time to "evolve"? Am I the only one who sees the vanity in this reasoning?

What vanity is there in doing it right in the first try? It is a very interesting achievement, one that relies not on the blind luck of evolution but on the application of a limited set of rules.

If evoultion worked like this, perhaps our retinas wouldn't be turned inside out as the currently are (for example).

How about we stay quiet until we can create a living thing from scratch that's more impressive than the life-forms the random unintelligent process of evolution has come up with.

Impressive is a subjective quality: while you may only find a whale-size elephant impressive, I find it quite impressive that someone has managed to do from scratch what evolution might only do after a relatively long time and probably with lots of inefficiencies and side-effects.

Re:Evolution does it again.... (0)

Anonymous Coward | about a year and a half ago | (#41930293)

What vanity is there in doing it right in the first try? It is a very interesting achievement, one that relies not on the blind luck of evolution but on the application of a limited set of rules.

If evoultion worked like this, perhaps our retinas wouldn't be turned inside out as the currently are (for example).

Without even questioning your unsubstantiated claim that our retinas are turned inside out, are flawed and could be better designed - isn't what's "right" or "correct" here also subjective by your own argument? Why is it that we can so easily critique something we don't fully understand, and the have the arrogance to presume, based on our limited understanding that it could be made better, without actually demonstrating it?

If anything, an evolutionist should argue that the best design to gaurantee our survival is what we currently have because all the other randomly generated attempts failed.

Impressive is a subjective quality: while you may only find a whale-size elephant impressive, I find it quite impressive that someone has managed to do from scratch what evolution might only do after a relatively long time and probably with lots of inefficiencies and side-effects.

What can I say, you're either easily impressed or helplessly delusional. Even the article presents the same argument and tries to justify their work to make it seem less vain:

One might wonder how designing a new protein from scratch could be better than starting with natural proteins, given the head start that nature has in evolving effective functions and stable conformations. In fact, evolution has honed the structures of many proteins so precisely that it can be difficult to get the backbone to budge into another conformation to accommodate a new function.

Re:Evolution does it again.... (1)

gomiam (587421) | about a year and a half ago | (#41930483)

...unsubstantiated claim that our retinas are turned inside out...

What would you call a retina that has the photoreceptors hidden behind the axons and the blood vessels so the blood vessels and the axons are inside the sphere area corresponding to the photoreceptors? Compare it to the octopus eye which has no extra layers between the light and the photoreceptors.

...are flawed and could be better designed - isn't what's "right" or "correct" here also subjective by your own argument?

They are flawed since they could be much more efficient "just" by having the layers in the right order, as in cephalopods. It just happens that evolution didn't have a plan at all (that's what evolution does, anyway) and, when animals needed better night sight, patches like reflective areas in the front of the eye had to be evolved, because turning back and redoing it all again wasn't an option any more.

If anything, an evolutionist should argue that the best design to gaurantee our survival is what we currently have because all the other randomly generated attempts failed.

It is the least worst that survived, not the best. If it was the best we would copy it down to the details, and I know of no artificial camera that puts anything between the lens and the photosensible material that isn't really needed there. At least, I don't know of any camera with a blind spot designed into it.

What can I say, you're either easily impressed or helplessly delusional. Even the article presents the same argument and tries to justify their work to make it seem less vain

I'm sure qualifying people so easily that helps your arguments a lot. Anyway, I find it impressive because it certainly isn't easy: otherwise someone would have probably done it decades ago. And, if the article tries to make it less vain, please tell me, why on Earth did the previous AC (I can't tell whether it was you) write this?:

Now we're invited to celebrate the achievement/intelligence of these ones who managed to fold a simple protein that would have folded itself into something far complex and useful, given enough time to "evolve"?

Either the article is celebrating an achievement and the quote is right, or it isn't as you write now and the quote was wrong, your choice :)

Re:Evolution does it again.... (0)

Anonymous Coward | about a year and a half ago | (#41941117)

Mark my words, it's only a matter of time before someone discovers that what were previously thought to be imperfections in the design of the eyes of vertebrates actually make it far superior to the octopus eye....the research just hasn't been done yet. Just like the so call "junk DNA" that evolutionist of the 1990s were leaning on, insisting that it supports Darwinism. Now the ENCODE project has found much of what was previously considered junk DNA provide important functions (albiet not protien coding).

So, be careful what you accept as science fact. I respect science and research but some of this stuff is just the opinion of arrogant men who are obsessed with their own ideas of how things should be (i.e. they are delusional). Remember Fred Hoyle?

--- we admit that natural things have a design, yet we deny there being a designer....oh the vanity of man.

Re:Evolution does it again.... (1)

gomiam (587421) | about a year and a half ago | (#41945857)

Mark my words, it's only a matter of time before someone discovers that what were previously thought to be imperfections in the design of the eyes of vertebrates actually make it far superior to the octopus eye...

Excuse me if I don't hold my breath. I'm not an octopus, mind you ;)

I respect science and research but some of this stuff is just the opinion of arrogant men who are obsessed with their own ideas of how things should be (i.e. they are delusional). Remember Fred Hoyle?

What would you need to not consider it "just the opinion of arrogant men"? Actually, I think that considering the human/mammal eye to be suboptimal shows more humbleness than arrogance, at least if you consider the millennia during which humans have asserted their being at the cusp of everything. And then it was discovered that the Earth wasn't the center of the solar system, that the solar system wasn't the center of the universe... I really think that finding out that the human is inherently suboptimal is quite humble. But that's just my opinion.

Re:Evolution does it again.... (0)

Anonymous Coward | about a year and a half ago | (#41930797)

You don't really seem to understand evolution, nor random search. Go study and come back.

Enzymes (1)

Anonymous Coward | about a year and a half ago | (#41930025)

Next step: understand how specific conformations perform their magic in accelerating chemical reactions by factors of trillions so we can design custom enymes.

Re:Enzymes (0)

Anonymous Coward | about a year and a half ago | (#41931809)

This task has been a major area of research for decades.

hello -- (4, Informative)

GPierce (123599) | about a year and a half ago | (#41930143)

This is actually a fairly important discovery. The poster of the article seems to be completely clueless as to why it is important.

Without going into all of the details, being able to predict the shape of proteins is one of the things needed to make nanotechnology fulfill its potential - to build a nanotech "assembler".

If you want all the details you would have to go back to "Engines of Creation" by Eric Drexler.

Proteins of the right shape can be used to create complex structures - anything from a virus to a nano-computer. Construct some RNA, feed it into a cell and get back as many copies of the protein chain as you please.

Do this for several different proteins.

Leave all of these proteins in the same chemical soup and they will combine on their own to form the more complex structuresl

But if you can't predict the shape the protein folds into, you can't get started. This has been a key problem in nano-tech going back to the 1970s.

Re:hello -- (2, Interesting)

Anonymous Coward | about a year and a half ago | (#41930353)

If this happens this could open up a new era in medicine.
It is literally *the* cure for hiv , cancer and just about everything else. Specific proteins can be created to attach to and kill exactly just about anything , it's the perfect artificial immune system.
The gloomy side of this is that it will also open up the door for new weapons. One could theoretically build proteins designed to kill exactly one individual potentially without leaving much of a trace to the untrained eye.

Re:hello -- (0, Insightful)

Anonymous Coward | about a year and a half ago | (#41930365)

Ya blah blah blah blah. If at least they could make proteins we could eat, now THAT would be a major achievement. But I suppose if it can't make any corporations rich then we won't see such a thing. Bring on the damned nano crap then.

Re:hello -- (0)

Anonymous Coward | about a year and a half ago | (#41934759)

If at least they could make proteins we could eat,

Why bother? If they did, you would just whine about how the evil corporations are killing us with GMOs and such.

Re:hello -- (1)

mapkinase (958129) | about a year and a half ago | (#41933879)

Shaping is nothing in proteins. Function is everything.

Re:hello -- (1)

Daniel Dvorkin (106857) | about a year and a half ago | (#41934495)

Shaping is nothing in proteins. Function is everything.

And proper function generally requires the proper shape, duh.

Re:hello -- (0)

Anonymous Coward | about a year and a half ago | (#41934657)

Except one doesn't know what shape gives the require function. Its more than just shape, one also has to design the active site within a pocket of the shape.They are not designing any function, just shape. An accomplishment indeed but still not quite there.

Re:hello -- (1)

mapkinase (958129) | about a year and a half ago | (#41941909)

No.

Re:hello -- (1)

Daniel Dvorkin (106857) | about a year and a half ago | (#41943305)

No.

So sickle-cell is caused by ... what, exactly, an imbalance of bodily humours?

Re:hello -- (1)

mapkinase (958129) | about a year and a half ago | (#41948791)

TIM-barrels

Re:hello -- (1)

mapkinase (958129) | about a year and a half ago | (#41948807)

>sickle-cell

Here is homework for you, newbie:

1/ read the Wikipedia article on sickle cell anemia
2/ read the fricking original article

This is really important (5, Interesting)

Anonymous Coward | about a year and a half ago | (#41930497)

I've always said that protein engineering will become more important to humanity than the transistor, For just one example of the incredible potential proteins have, look at enzymes. These are biological catalysts that tirelessly perform very specific chemical reactions. In the case of some enzymes, they are called 'kinetically perfect', meaning that they are so fast the only way we have of explaining the reaction speed is that every time the molecule they work on collides with the enzyme, the reaction immediately happens. Mind-blowingly, some enzymes are even faster than this, so-called 'better than kinetically perfect' and how they manage their astounding speed is one of biology's great unsolved problems.

Some other cool example of proteins: Proton pumps in your stomach, which carry individual protons into your stomach to make acid. Photosystems 1 and 2 in plant chloroplasts, which juggle electrons between each other and weave sunlight into sugar, forming the basis of the whole earth's food chain.

Re:This is really important (1)

Anonymous Coward | about a year and a half ago | (#41931201)

Photosynthesis is achieved by having a very specialized enzyme that works like a workshop bench. It clamps down the hydrogen bonds of the H2O molecule and literally snips off the hydrogen atoms using the energy from several UV photons. All done using the electrical charges of chemical bonds and free electrons.

Re:This is really important (1)

mcgrew (92797) | about a year and a half ago | (#41932157)

In the case of some enzymes, they are called 'kinetically perfect', meaning that they are so fast the only way we have of explaining the reaction speed is that every time the molecule they work on collides with the enzyme, the reaction immediately happens. Mind-blowingly, some enzymes are even faster than this

So... thiotimoline is an enzyme? Biochemist Dr. Asimov was wrong about its composition?

Re:This is really important (1)

interkin3tic (1469267) | about a year and a half ago | (#41932393)

I remember hearing that DNA polymerase runs so fast along DNA that if it were a train, and the base pairs were railroad ties, it would be moving something like a thousand miles an hour. And it would be duplicating the train tracks nearly perfectly as it did so.

Re:This is really important (2, Informative)

Anonymous Coward | about a year and a half ago | (#41932869)

I don't think OP did a great job of explaining kinetic perfection, so I'll try to expand on it.

Firstly, I've generally heard it referred to as catalytic perfection, not kinetic. Regardless, it means that

1) every enzyme-substrate collision is productive, that is, generates a product and
2) the reaction happens in less time than the enzyme and substrate can find each other in solution.

This means that the "limiting reagent" of the reaction is the diffusion speed of the enzyme and substrate - if enzyme and substrate(s) could encounter each other in less time, they would (might) react faster. Some enzymes can surpass this limit by having an arrangement of charged amino acid residues on the surface that creates an electric field about the active site which accelerates the substrate toward the enzyme, causing it to move faster than the diffusion limit. It also serves to orient the substrate properly (ie, negatively charged portion of substrate moves toward positive portion of the enzyme, etc), ensuring that the substrate lines up properly in the active site for optimal catalysis.

I wouldn't say that "how they manage their astounding speed is one of biology's great unsolved problems," because such a statement is an extreme oversimplification of the problem. Many enzymes use catalytic mechanisms that are completely different from each other, and as a result, there isn't a general solution to explaining the rate enhancements that they afford. There are many factors that enzymes combine to enhance reaction rates though, such as stabilizing the transition state, correctly orienting substrates, and so forth. Some of these are well understood conceptually, but how they play a role in specific proteins is not. However, many catalytic mechansims are reused, so figuring out how one enzyme works may help to elucidate the mechanism of similar enzymes. But it also may not. For example, class I and class II aldolases have entirely different mechanisms (one has metals in the active site, the other does not).

Regardless, I agree with your assessment of the importance of the enzymes as molecular factories. I am very excited to see what the future holds.

Nobel Prize material!!! (1)

G3ckoG33k (647276) | about a year and a half ago | (#41930569)

Congratulations, in advance!!!

The other day I reflected over the lack of knowing how these foldings work; I recalled some tv program for the 70s that had identified this as a big issue back then Voila, today we have a working progress.

Nobel Prize material, indeed!!!

Proteins (1)

MoonPyramid (2771071) | about a year and a half ago | (#41930575)

chains of amino acids that fold spontaneously into a precise conformation, time after time

I've seen this happen in many Japanese movies before, the Japanese do have a way to make proteins always hit the same spots from a distance.

Proteins to order? (1)

Muad'Dave (255648) | about a year and a half ago | (#41930909)

Ok, I'll have 500g of Bovine Psoas Major proteins, preferably with some cured porcine abdominal protein wrapped around it.

Let me guess... (2)

Type44Q (1233630) | about a year and a half ago | (#41930967)

...has designed five proteins from scratch that fold reliably into predicted conformations.

Let me me guess:

One is a potent carcinogen.
One causes deadly priapism [wikipedia.org]
One causes thick hairgrowth... inside your body.
The two others are considered really dangerous. :p

mmm... new meat (0)

Anonymous Coward | about a year and a half ago | (#41931173)

Forget frankenmeat cow, now you can make meat that's never existed in nature. "Hmmm... I call this... Zerg Steak."

Re:mmm... new meat (1)

Sulphur (1548251) | about a year and a half ago | (#41933597)

Forget frankenmeat cow, now you can make meat that's never existed in nature. "Hmmm... I call this... Zerg Steak."

Second steak because it cooks so fast.

And then the a the zombie prion escapes (1)

dywolf (2673597) | about a year and a half ago | (#41931451)

Here it comes!

Will they print prions? (0)

Anonymous Coward | about a year and a half ago | (#41931543)

Only terrorists print proteins, because they can could be used to create outbreaks of bovine spongiform encephalopathy
http://en.wikipedia.org/wiki/Prion [wikipedia.org]

David Baker, you wonderful man (3, Informative)

Anonymous Coward | about a year and a half ago | (#41931553)

I used to work in a protein engineering lab that collaborated extensively with Baker's lab. Let me be the first to say the quality of work coming out of there is outstanding. Protein engineering is incredibly difficult and their Rosetta software (protein folding again) is pretty much essential (yeah yeah, there's other software and rosetta has flaws, like not taking charged amino acids into account, but really its the best we have) -- even more so than pymol for any design you'd be doing.

  This is the second large break through coming from them in the past few years. The other one was designing enzyme that performed a totally novel reaction. Details here: http://www.sciencemag.org/content/329/5989/309 . I really can't stress how big of a deal this is for designed (chemical) molecules. Even if the reaction wouldn't have happened under normal conditions or without causing decomposition to the rest of the molecule, you can make an enzyme that will do it for you.

This study should help the creation process, generally directed design runs into a lot of problems with proteins that no longer fold. Being able to determine computationally what has a chance of working would greatly speed up the process. Beyond that congrats to the lab and one of the most hands on, in the science PIs I know

Re:David Baker, you wonderful man (0)

Anonymous Coward | about a year and a half ago | (#41939191)

You could help if you have a computer http://boinc.bakerlab.org/rosetta/

Boffers! (0)

Anonymous Coward | about a year and a half ago | (#41933191)

Given the rapid pace of new and amazing announcements, have we reached the knuckle in the exponential curve of scientific development?

fold.it? (1)

meridoc (134765) | about a year and a half ago | (#41934035)

This is awfully cool!
According to the article, they used Rosetta@home for some predictions. I wonder if they've also tried fold.it [fold.it] , especially since that project is also out of U of Washington.

You can help with these efforts! (0)

Anonymous Coward | about a year and a half ago | (#42002933)

I work in the Baker Lab, and work like this relies on the processing cores of thousands of people around the world. The structure of every protein designed in this paper were determined using a computer very much like the one you're probably using to read this. If you would like to donate your unused CPU cycles, it would be a great (and direct) help for advancing the field of protein design and structure prediction -- please visit http://boinc.bakerlab.org/rosetta/ to sign up. And if you're interested in helping out to develop new strategies for protein structure prediction, try fold it (http://fold.it/portal/)

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