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Biotech News

Creating Artificial Proteins 180

Posted by samzenpus from the make-me-a-new-hand dept.
Spy der Mann writes "By examining how proteins have evolved, UT Southwestern Medical Center researchers have been able to design genes to create artificial proteins. The researchers have discovered a set of simple "rules" that nature appears to use to design proteins. By feeding these rules into a computer program, they were able to obtain a sequence of artificial genes. These genes were then inserted into laboratory bacteria, producing the artificial proteins as expected."
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Creating Artificial Proteins More

Creating Artificial Proteins

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  • That's nothing (Score:5, Funny)

    by Mateito ( 746185 ) on Wednesday September 21, 2005 @10:11PM (#13618833) Homepage
    I've been creating proteins by hand since I was 12!

  • We're learning the words... (Score:4, Funny)

    by FlyByPC ( 841016 ) on Wednesday September 21, 2005 @10:12PM (#13618840) Homepage
    Hopefully we'll figure out what not to say while learning the grammar, style, and syntax of this new language. It's a bit worrying -- but this really has a lot of potential, I think!

  • Tinfoil hat, but... (Score:1, Interesting)

    by USSJoin ( 896766 )
    This seems like a very, very simple way of tagging people. I.E., if you can make a protein that can't occur in the body naturally, inject it into someone when you do something to them. Kind of like having the P on the wrists of pirates, except it avoids all those "social stigmatization" arguments... but allows foreign governments (or whoever) to see that they've been marked. Interesting....
    • I dunno ... an embedded RFID tag in your forehead would probably be cheaper.

    • Re:Tinfoil hat, but... (Score:5, Funny)

      by Anonymous Coward on Wednesday September 21, 2005 @10:20PM (#13618875)
      Good lord, what if people had other unique markings that could be tracked... finger/palm prints, DNA, retinas... now THAT would be scary.

      Oh wait.

    • Re:Tinfoil hat, but... (Score:5, Insightful)

      by xanthines-R-yummy ( 635710 ) on Wednesday September 21, 2005 @10:47PM (#13619019) Homepage Journal
      Most proteins eventually degrade, if they are not immediately destroyed by the immune system (ie, antigenic). Furthermore, for proteins that don't degrade quickly, how would you detect these proteins? Other than putting radioactive isotopes (try getting on an airplane with that in today's environment!), I don't see how you would detect them other than strapping someone down and getting some blood. I suppose you could always try a gene therapy technique to continually express protein, but gene therapy is still highly experimental and presents its own problems. This sounds way more complicated than just implanting inorganic RFID chips/beacons/whatevers under the skin or in a (cough!) body cavity.
      • "Strapping someone down and getting some blood" is exactly what I had in mind, actually. If every time you bring someone in for questioning-- say in a foreign country, without access to U.S. fingerprint records, etc-- you take some blood, and you find these marker proteins in them, you still know they are a serial killer / rapist / terrorist / whatever, even though you don't have access to the records. Again, like the P brand; even before you write back to merry old England, you know you have a pirate.

        As fo
      • Uhhh, its actually quite amazing how radioactive you can be and still "pass inspection." I had a cat who had I-131 treatment for hyperthyroidism, and the radiologist(s?) that treated her kept telling me that if people really knew how much radiation you could have pumped into you (and then immediately go fly on a plane next to a pregnant person, infant, 100 year old, cat, etc...), people would probably freak.

        The dosage they give (which would be proportionatly bigger per mass) is the aformentioned "legal limi
      • Wouldn't the body destroying the marker be good for this technique?

        If the body does destroy it, you could detect who was marked by the specific antibodies that stay in thier blood.

        The protein doesn't stay, but just like pepridge farms, the imune system remembers.

  • I hate to turn this into a flamewar so soon, but.. (Score:5, Insightful)

    by kyle90 ( 827345 ) <kyle90@gmail.com> on Wednesday September 21, 2005 @10:17PM (#13618862) Homepage Journal
    Isn't one of the reasons that creationist use when they attack evolution (actually abiogenesis) is that it would take such a long time to generate functioning proteins through random chance that it would be statistically impossible? If there are simple "rules" to create proteins, maybe that's how nature was able to come up with life so quickly.

    • Re:I hate to turn this into a flamewar so soon, bu (Score:5, Informative)

      by salemnic ( 244944 ) on Wednesday September 21, 2005 @10:23PM (#13618892)
      I think you might be using backwards logic here. TFA states that by examinig 100 proteins they were able to notice some standard common things about the proteins they were looking at. When they made rules around those common things they could make new proteins.

      It's like having 100 pieces of example code to look at before trying to create your own, not generating the code from nothing.

      s
      • They looked at 100 proteins to learn what the simple rules are. That does not preclude the existence of rules that are simple. GP was right, if simple rules exist (no matter how we learned what they are), then it is more likely that proteins could arrise by chance, than if the simplest rules for making proteins are complex.
        • I'm not sure how simple the rules are has anything to do with the chance that a particular thing arises. A simple rule could be "A standard earth protein must have 37 XYZ chains" - short, sweet, and simple. But how does now knowing that there must be 37 XYZ chains to get a standard protein now mean that before it was known it was simple? Especially when there are more potential combinations than there are atoms in the universe.

          I stick by my earlier assertion that simple rules are only simple after they a
      • Scientists don't use evolution because they're out to win some sort of ideological battle. They use it because it works. They want to understand how an amino acid becomes a protein. Evolution helps explain the process. Creationism and ID don't explain the process at all. They just say two things: (a) god made them; and (b) stop asking questions.

        If evolution didn't help further science, it would be abandoned in favor of whatever did. But it works, which is why scientists rely on it and why teachers nee
        • Actually progress in science has been suppressed in some areas by scientists. And it's engineering that will fail and try other things. If the wings don't work you don't burn a chicken you design better wings.
        • That's a fairly... simple, and incorrect, view of creationism and ID. All ID says is that the starting point of the universe is so complicated, that it could not happen from chance. ID usually says nothing about the science between then and now, and doesn't ask the observer to stop asking questions.

          There is a very vocal minority that does think the way you are suggesting, but most people who believe in Creation also believe in science, and most religious people don't believe their respective holy books ar

    • Re:I hate to turn this into a flamewar so soon, bu (Score:5, Interesting)

      by haluness ( 219661 ) on Wednesday September 21, 2005 @10:24PM (#13618895)
      And the answer to this could be that a lot of rules have been randomly tried out. It turns out that the rule(s) we are seeing/discovering are the ones that lasted - and if they are simple they are probably efficient in some way.

      The creationist/ID policy is to avoid facing unknowns by passing the buck onto a designer. In the current example, just because something appears elegant and simple to some person, it does'nt mean that it could not have naturally occured.

      Our jobs, as scientists, or in the more general case, as people with a scientific temperement, is to uncover how or why this simple and elegant thing is the way it is - not to say, 'It's too tough, lets pass the buck onto the designer'!
      • i have no comment other than 'word', very well put.
      • The creationist/ID policy is to avoid facing unknowns by passing the buck onto a designer. In the current example, just because something appears elegant and simple to some person, it does'nt mean that it could not have naturally occured.

        I don't think that's quite correct. My understanding is that ID examines a result using statistical or logical tools to see if it could have occurred by chance. It's not a subjective test. A statistical abberration indicates some outside influence. A collection of pr
        • Evolution is both incremental, but also quasi-static due to being driven by the environment. Genetic change builds up in a population over time giving rise to minor varieties none of which likely have an overwhelming advantange. At some point the environment changes - a famine, the arrival of a competitor, a change in temperature, etc, and now in an instant the advantage/disadvantage of these previously benign accumulated varieties/changes becomes apparant, and the evolutionary record shows the population "
        • The problem with that way of looking at things is that, unfortunately for ID, anything which is statistically improbable can happen by chance, by definition.

    • Re:I hate to turn this into a flamewar so soon, bu (Score:1, Informative)

      by Anonymous Coward
      Their "rules" were derived from observing nature, not computed or by any ab-initio means.

      The original summary of the article is quite off base, as many of these biochemistry-related revelations are.

      I would better summarize the Nature paper as saying that the researchers have found a somewhat reliable method of duplicating a three-dimensional structure by using existing sequences as a simple template. The concept of truly "designing" a protein from scratch remains the Grail of this field.
    • What it is more likely to imply is that many (maybe all?) proteins seem to share the same basic "rules" in their construction, therefore nature only had to come up with a few workable combinations, and everything else was developed from that.

      Note that these "rules" are defined by the scientists based on observation and not necessarily actual, natural restrictions. A lot of creationists seem to fall into that trap when defining species - the concept of "species" is a completely man-made concept and actually
      • >the concept of "species" is a completely man-made concept and actually rather arbitrary. Nature does not make any such distinction.

        Not true species, is the only testable (ie scientific, ie non-arbitrary) classification. All the rest are arbitrary. A species is defined as a population of organisms which have reproductive isolating mechanisms which prevent the production of a viable (including sexual) offspring. ie two organisms are members of a different species when they are unable to reproduce and/or

    • "If there are simple "rules" to create proteins, maybe that's how nature was able to come up with life so quickly."

      OK...but who/what is nature to develop/come up with these rules? The argument your trying to debunk is that they couldn't be created by chance....there is nothing chance about having "rules" to create proteins...and for that matter...order.
    • Every time someone uses experiments like this to "disprove creationism" (as if this is something that can be proven or disproven in the first place), they ignore the common feature to all of these tests:

      The scientist.

      All this "proves" is that it is possible for an intelligent being to combine elements to create something more complicated.

      You're saying this experiment shows all of this around us "proves" it could all happen on its own?
      • Actually what this supports is the rather obvious but profound fact that evolution happens on many levels. Not only are DNA changes that directly support the individual beneficial, but so are changes that support more rapid evolution. If encoding for proteins has evolved into a simple scheme so that changes generate a higher proportion of fucntioning proteins, then evolution is speeded up.

        This is why creationist arguments fall flat on their face - because they don't argue against evolution as theory posits
    • "If there are simple 'rules' to create proteins, maybe that's how nature was able to come up with life so quickly."

      Well, first it is sometimes easier to reverse engineer than create. Second, it is also possible to use these 'rules' to support intelligent design. I mean, if "God" were to create life and all that, wouldn't he create an easy-to-replicate manufacturing process?
    • Creationists also like to argue that no true value comes out of studying evolution and that it is proven to be false and ignore the fact that the basic principles of evolution play an enormous role in helping us further understand biochemistry and molecular biology.
    • ...is that it would take such a long time to generate functioning proteins through random chance that it would be statistically impossible

      You existing is "statistically impossible", but obviously you are observing you exist as you read this.

      Given enough time... Anything is possible, but the most probable thing will happen... Or something... I don't think the human mind can really comprehend what happens in the universe over 10 billion years.

      You know what they say about infinite monkeys with infinite amount [wikipedia.org]

  • Name that film... (Score:5, Funny)

    by moviepig.com ( 745183 ) on Wednesday September 21, 2005 @10:22PM (#13618885)
    From the article: The real test will be to put [the new proteins] back into fruit flies...

    "Hel-l-l-p me-e-e-e-e..."

  • Creating artificial drugs (Score:4, Informative)

    by Khyber ( 864651 ) <techkitsune@gmail.com> on Wednesday September 21, 2005 @10:23PM (#13618890) Homepage Journal
    Well, we know we've been able to modify DNA to produce insulin from bacteria.

    We've got bacteria that crap out metal wires (Can't remember if we discovered them or made them)

    Now where's the bacteria that will make substances like xanax or other drugs, so it can make the entire market cheaper and more affordable to those who need it but don't have insurance, and "naturally" at that? (Naturally as in not needing a buttload of power from a processing plant for the drug and wasting energy uselessly)
    • I invented it already .. Xanaxus Screwmasterus.

    • Re:Creating artificial drugs (Score:5, Informative)

      by k98sven ( 324383 ) on Wednesday September 21, 2005 @10:34PM (#13618944) Journal
      Now where's the bacteria that will make substances like xanax or other drugs, so it can make the entire market cheaper and more affordable to those who need it but don't have insurance, and "naturally" at that? (Naturally as in not needing a buttload of power from a processing plant for the drug and wasting energy uselessly)

      Um.. news flash: Drugs have been made that way for years.

      But first: This works for proteins such as insulin. Most drugs are not proteins, however.

      And for those who are, there is nothing about it which necessarily makes it cheaper or less power-consuming. Bacteria need food. Bacteria need to be kept warm. And most importantly, you've got to seperate and purify your drug from the bacteria and growth substrate and whatnot.

      Of course, for proteins you've got no choice. It's practically impossible to synthesize proteins using conventional chemistry. And it's very very difficult (and likely uneconomical) to use bacteria to produce other organic compounds. So these things are complimentary to eachother, really.

      • But first: This works for proteins such as insulin. Most drugs are not proteins, however. And for those
        who are,

        I take exception at your humanitizing of proteins

      • And it's very very difficult (and likely uneconomical) to use bacteria to produce other organic compounds.
        Many antibiotics are produced by bacteria. They aren't proteins.
        • Well, duh. But the point wasn't "bacteria can't easily make stuff which isn't a protein", the point was "bacteria can't easily be engineered to make stuff which isn't a protein".

          Those antibiotics-producing bacteria weren't engineered to produce antibiotics.
          (Although they are typically engineered to produce more antibiotics than in the wild, but enhancing function is pretty far from creating it.)

    • k98sven is spot on. However, something else to add is that bacteria are not humans and can't synthesize some human proteins. Especially complex ones that have disulfide bonds, complex quaternary structure (ie, multiple subunits), inorganic subunits, modifications such as phosphorylation, glycosylation, etc etc etc. Bacteria have limitations and are not the end-all, be-all solution to our biomedical/pharmaceutical problems.

      Sorry to be geeky, but this is the science section, isn't it?

    • Now where's the bacteria that will make substances like xanax or other drugs, so it can make the entire market cheaper and more affordable to those who need it but don't have insurance, and "naturally" at that?

      A sibling correctly notes that they already do that. And to answer a similar question (why hasn't it created cheaper and more affordable drugs), you'd have to know that engineered bacteria that produce such useful compounds are often patented. I feel that patenting living organisms is even worse tha
      • The thing is, they're not so much patenting the particular organism as much as the specific genetic sequencing they've done to the host to produce whatever protein they're after.

        It costs billions of dollars worth of investment to set up the lab conditions, hire the researchers, test, retest, and maybe sacrifice a chicken or two to Jobu to even come up with ONE protein with any kind of pharmaceutical benefits. Not only that, but now you've gotta make sure you can obtain enough of this thing to sell, purify
    • Jay Keasling at UC Berkeley is doing this.

      In a nutshell Prof. Keasling and these guys [amyrisbiotech.com] are getting E. coli. to make terpenoids [wikipedia.org] cheaply and in large quantites. The first commercial application that amyris is developing is a process for artemisinin, a fantastic anti-malarial drug. Currently, the drug can only be extracted from some plant in small amounts. This bio-synthetic process will (hopefully) lower the cost per dose from ~$USD 2.40 to ~$USD 0.25 (iirc).

      Somewhat off topic, but probably still interesti

  • Let's not get ahead of ourselves here.. (Score:5, Insightful)

    by k98sven ( 324383 ) on Wednesday September 21, 2005 @10:24PM (#13618898) Journal
    The researchers believe they may have found a set of statistical rules for determining the tertiary ('overall') structure of proteins from the sequence.

    (Although the summary reads otherwise, creating a 'new' protein with an arbitrary amino acid sequence isn't new at all though. )

    If this pans out, it is of course significant towards the goal of engineering 'new' proteins one day. But there is still a lot to be covered. Even if the relationship between sequence and structure were simple and known (and it isn't, yet), you still have the issue of relating structure to function.

    Which isn't known. And of course, even knowing the structure and function of a single protein doesn't mean you know what it's going to do in a complicated environment such as a cell, where there are thousands of things to interact with.

    It's a step forward, nonetheless. But if someone thinks this means we're going to be tricking-out living organisms with new custom-engineered proteins anytime soon, you'll be disappointed.

  • Almost there! (Score:4, Interesting)

    by superub3r ( 915084 ) on Wednesday September 21, 2005 @10:27PM (#13618907) Homepage
    Artificial proteins! YES! One step closer to Artificial steak!

  • Information Theory Usages? (Score:5, Interesting)

    by Frumious Wombat ( 845680 ) on Wednesday September 21, 2005 @10:30PM (#13618919)
    Can this be used for information compression in any way? After all, it was discovered about 20 years ago that simple fractal equations gave shapes very much like ferns. This could give you a shorthand way of compressing the genome of an organism, then making comparisons.

    It would also, of course, be interesting if you could use this to work backwards through the genome to a set point, and (hypothetically) bring back the Auroch.

    Personally, I want to see how this deals with metal incorporation at the active site, and whether their selection rules work for that as well.

    • Re:Information Theory Usages? (Score:5, Funny)

      by ScrewMaster ( 602015 ) on Wednesday September 21, 2005 @10:59PM (#13619059)
      Yes, a protein computer operating in meat-space would hold a lot of advantages over silicon ... until your dog got hold of it. Still, it would make a great excuse for not doing your homework, "I'm sorry, Miss Smith ... my dog ate my computer."

    • It would also, of course, be interesting if you could use this to work backwards through the genome to a set point

      There actually is research that looks at predicting the last common ancestor between two species. For example, given man and ape, you can make a prediction on what the man/ape gnome was before they diverged into two species (not to go into details, but a lot of species divergence is the result of some kind of large scale chromosome rearrangement that makes it impossible to sexually reproduce).

  • I only have one question. (Score:4, Funny)

    by phxhawke ( 35260 ) on Wednesday September 21, 2005 @10:36PM (#13618955) Homepage Journal
    How long before gcc supports this new instruciton set? :p

  • Link to Nature article (Score:5, Informative)

    by JuliusSu ( 139796 ) on Wednesday September 21, 2005 @10:37PM (#13618964)
    Full text of article [nature.com], institutional/personal subscription required.

    Abstract: Classical studies show that for many proteins, the information required for specifying the tertiary structure is contained in the amino acid sequence. Here, we attempt to define the sequence rules for specifying a protein fold by computationally creating artificial protein sequences using only statistical information encoded in a multiple sequence alignment and no tertiary structure information. Experimental testing of libraries of artificial WW domain sequences shows that a simple statistical energy function capturing coevolution between amino acid residues is necessary and sufficient to specify sequences that fold into native structures. The artificial proteins show thermodynamic stabilities similar to natural WW domains, and structure determination of one artificial protein shows excellent agreement with the WW fold at atomic resolution. The relative simplicity of the information used for creating sequences suggests a marked reduction to the potential complexity of the protein-folding problem.

    From this page [embl-heidelberg.de] : a WW domain is the smallest, monomeric, triple-stranded, anti-parallel beta-sheet protein domain that is stable in the absence of disulfide bonds, cofactors or ligands.

  • Stupid article (Score:4, Interesting)

    by MillionthMonkey ( 240664 ) on Wednesday September 21, 2005 @10:44PM (#13619007)
    Why can't these articles include any meaningful information? They refuse to tell you what they're about.

    Earlier research has shown that for a given group of related proteins, or protein family, all family members share common structures and functions.

    What would be an example of a "protein family" in this context? Filamentous? Membrane associated? Globins? Antibodies? No idea. "Common structures and functions" could mean several different things.

    By examining more than 100 members of one protein family, the UT Southwestern group found that the proteins share a specific pattern of amino acid selection rules that are unique to that family.

    This tells us nothing that isn't already known. Of COURSE proteins with related functions share specific patterns of amino acid selection rules or they wouldn't work. WHAT sort of selection rule did this group actually find?

    "What we have found is the body of information that is fundamentally ancient within each protein family, and that information is enough to specify the structure of modern-day proteins," Dr. Ranganathan said.

    He sounds like he's talking to a little kid.

    He and his team tested their newly discovered "rules" gleaned from the evolutionary record by feeding them into a computer program they developed. The program generated sequences of amino acids,

    and how did it do this?

    which the researchers then "back-translated" to create artificial genes.

    i.e. they did a trivial replacement of single amino acid letters with three letter codons in silico, then generated the corresponding DNA sequence.

    Once inserted into laboratory bacteria, the genes produced artificial proteins as predicted. "We found that when isolated, our artificial proteins exhibit the same range of structure and function that is exhibited by the starting set of natural proteins," Dr. Ranganathan said. "The real test will be to put them back into a living organism such as yeast or fruit flies and see how they compete with natural proteins in an evolutionary sense."

    Translation from stupid-articlese: in vitro the translation products of the artificial DNA folded into shapes similar to wild type proteins. I think.

    One can only assume that these guys chose proteins that don't undergo post-translational modification.
    • Synthetic prions, anyone?

    • Re:Stupid article (Score:5, Insightful)

      by QuantumG ( 50515 ) <qg@biodome.org> on Wednesday September 21, 2005 @11:06PM (#13619089) Homepage Journal
      In two papers appearing in the Sept. 22 issue of the journal Nature, Dr. Rama Ranganathan, associate professor of pharmacology, and his colleagues detail a new method for creating artificial proteins...

      That's the sum total of useful information in the article. Go read the full paper in Nature if you want to know more. Scientific reporting at its finest. Now and then I read an article where a "journalist" actually understands what has been written and has something profound to say about it that the scientists themselves didn't even think of (and actually agree with). Unfortunately it's increasingly rare these days. Even rags like Scientific American seem to do more puff pieces and press releases than well researched articles these days.
      • Go read the full paper in Nature if you want to know more. Scientific reporting at its finest.

        I agree, the press release is useless. The take-home message of the Nature article itself (from a probabilistic modeling pov) seems to be that, in order to design WW proteins that folded stably, it was necessary to model covariation between residues, rather than just independent site-specific frequencies (as would, for example, be generated by a Hidden Markov Model). The particular covariation model is called

    • which the researchers then "back-translated" to create artificial genes. i.e. they did a trivial replacement of single amino acid letters with three letter codons in silico, then generated the corresponding DNA sequence.

      Entirely off subject, but I'd like to point out, that while ordering an entire gene might seem a little science fiction, you can basically order any sequence you want just by sending off a series of AGCT's through a web form today. In fact, it is entirely possible for someone to order

      • Ignorant Comment (Score:1, Informative)

        by Anonymous Coward
        Before there is a large debate in the ethics community, they (you) ought to get the facts straight.

        E. coli is not a virus. Depending on the strain, the genome size is anywhere from 4.6 to 5.2 millions of base pairs. Putting one of your very own E. coli genomes together would be difficult and expensive. Better yet, why not just grow some? They'll spit up their genome after a few biochemical steps at the lab bench. If you were talking about a phage, their genomes are variable, averaging 35-50 kbp, or tho

    • Re:Stupid critic (Score:3, Interesting)

      by Red Flayer ( 890720 )
      "This tells us nothing that isn't already known. Of COURSE proteins with related functions share specific patterns of amino acid selection rules or they wouldn't work""

      This cannot be assumed; while logical on the surface, that's like saying that porpoises and sharks must be from the same family because they both swim in the ocean and have the same body shape. The scientific method DEMANDS that a hypothesis like that is tested.

      "He sounds like he's talking to a little kid. "

      In terms of protein chemistr
  • Hey, I guess Intelligent Design was just ahead of its time.

  • hair (Score:2, Funny)

    by gcnaddict ( 841664 )
    maybe now all us anime/manga fans can rejoice and change the hair color of our kids to sky blue, sea green, or bubblegum pink, or some other outlandish color like purple

  • And this is news because? (Score:3, Interesting)

    by DrCJM ( 827451 ) on Wednesday September 21, 2005 @11:11PM (#13619107)

    If that was all they'd done I find it difficult to see how this differs from doing a multiple sequence alignment for a family of proteins, then making a gene for the consensus sequence.

    Checking the paper (and related News and Views article) in Nature itself (http://www.nature.com/nature/journal/v437/n7058/i ndex.html [nature.com] ) (subscription required) indicates they've done more than that. By including the effects of coevolution - where one position in the protein mutates in concert with another to maintain optimal contacts - they generate a substantially better algorithm for manufacturing particular folds. (ie: 25% success in achieving folding versus 0% for conservation alone. 60% presence of wild-type function in the 'designed' proteins.)

    Interesting, but I'm suprised it made it into Nature. (OK then, jealous...)
  • Mankind created happy little protein-building bacteria. And it was good.

  • Rephrasing the Story Description (Score:3, Informative)

    by Fractal Dice ( 696349 ) on Thursday September 22, 2005 @12:41AM (#13619320) Journal

    The rules for how DNA encodes protiens have been known since before I was born. The evolutionary mapping of how the genes coding different protiens duplicated and evolved into new structures is fairly easy to map out (give or take a brute force algorithm that runs in double-factorial-time to search through all evolutionary trees looking for the one that minimizes the number of mutations required along the way).

    So this group has calculated the most likely common ancestor of the gene that now codes for a whole family of protiens, encoded the solution in real DNA, stuck it into bacteria and shown that it actually does produce a protien that they have been able to isolate the actual protien so that they can explore what it does/did.

    (the term "articial protien" seems very odd to read - before I think it through, it sounds as though its hinting there is something mystical to "natural" protiens untouched by humans)

  • An interesting idea, but (Score:3, Interesting)

    by Nutty_Irishman ( 729030 ) on Thursday September 22, 2005 @01:07AM (#13619435)
    While I realize this news seems fascinating to some individuals, it is not something so entirely new that people in Computational Biology would consider it groundbreaking. Using the computer algorithms to generate new gene sequences is actually just a matter of running the gene finding algorithms you used to find these genes backwards (in fact, many people have been testing their gene finding algorithms by using their old algorithms to generate pseudo test sets). The only thing new about this paper is that people actually went forward and experimentally validated their results. An interesting find, however, the end result does not provide a huge leap to science.

    Now, if people are really interesting in some neat ways of reengineering genes back onto themselves, then they should take a look at some of the work being done with synthetic circuits. The beauty of synthetic circuits is that since you already know how the genes will function, it's just a matter of setting the circuit up in the fashion that you want so that it produces the end result that you want. There really is no limit to what you can do with synthetic circuits (of course, researchers have a long way to go before they master and understand all the regulatory mechanisms). For example (and these are all very theoretical examples): building a cell circuit to release a drug into a body in a very time released fashion (and perhaps autonomously renewing, for example, building a circuit to release insulin into the body given the sugar level of the individual), designing a circuit to recognize and destroy tumors (or perhaps an even simpler form of designing a circuit to recognize and fluorescently label tumor cells in the body helping in removal/early detection). Of course, one could also build quite malicious synthetic circuits as well. For example, a circuit that would aggregate to the wall of the heart and, after a certain number of other cells accumulate, triggering a signal to all the malicious cells and destroy the heart in unison.

    The other nice advantage of synthetic circuits is that the more we learn out regulatory mechanisms in species, the more we can use them for synthetic circuits. The more we use them for synthetic circuits, the more we understand about how exactly the underlying mechanism works (what causes them to break, how do they deal with differing toxic environments, etc). It creates a nice feedback loop with the progression of science.

    There will come a day where it will be useful to generate new DNA/Proteins in combination with synthetic circuits, but, as noted in a previous post, we don't understand the relationship between protein sequence and structure/function enough for it to be a viable option (and this is just with how the protein folds, we haven't even gotten in to the problem of gene regulatory structures-- multiple gene splicing, chromosome structure elements, binding motifs, translational regulation, etc). In fact, this area is something we probably want to venture into as it provides us with an even finer control over the rate constants for synthetic circuits. But for now, the generation of randomly generated genes based on prior genes will go overlooked for quite some time.

  • OH MAN I CANT WAIT FOR THE FUTURE! seriously, cyborg fish people with tentacles and hard drive implants, think about it.

  • Artificial? (Score:2, Interesting)

    by msormune ( 808119 )
    I do not pretend to be an expert, or actually know anything about the subject and to promote Slashdot standards on information digesting, didn't actually read the article. But if one creates proteins that are exactly as nature would manufacture the real thing, why are they called artificial? They are the real thing!

  • if anyone is interested in the algorithms used (Score:5, Interesting)

    by afodor ( 916643 ) on Thursday September 22, 2005 @01:45AM (#13619564)
    We published a series of papers evaluating correlated mutation algorithms, including SCA, which is the algorithm used in this pair of Nature papers. I haven't had a chance to look closely at the two new papers, but we found that SCA performed rather poorly when compared to other algorithms that calculate covariance from a multiple sequence alignment. SCA has a troubling tendency to assign high scores to pairs of columns of a multiple sequence alignment that have random sequence in them.

    PDFs of our papers, and Java code implementing 4 different correlated mutation algorithms including SCA, are at my web site:

    http://www.afodor.net [afodor.net]

    The references are:

    Anthony A. Fodor, Richard W. Aldrich. On Evolutionary Conservation of Thermodynamic Coupling in Proteins. JBC 279(18):19046-19050, 2004

    John P. Dekker, Anthony Fodor, Richard Aldrich and Gary Yellen. A pertubation-based method for calculating explicit likelihood of evolutionary co-variance in multiple sequence alignments. Bioinformatics 20:1565-1572, 2004

    Anthony A. Fodor and Richard W. Aldrich. Influence of Conservation on Calculations of Amino Acid Covariance in Multiple Sequence Alignments. Proteins 56(2): 211-221, 2004

    The last paper contains a comparison between SCA and three other correlated mutation algorithms.

    As I said, I haven't had a chance to look carefully or critically at the new papers. (It takes me a LONG time to read a paper critically :-> This Slashdot thread will be likely long archived before I finish thinking about these papers!). But this particular algorithm aside, people who are interested in bioinformatics and contact prediction may find the math behind the correlated mutation algorithms interesting.

    Anthony

    Email: anthony.fodor(remove this and put in an at symbol)gmail.com
    http://www.afodor.net/ [afodor.net]

  • A cure for psoriasis (Score:4, Interesting)

    by infinite9 ( 319274 ) on Thursday September 22, 2005 @09:24AM (#13620797)
    I've been on enbrel for six months now to treat my psoriasis (think lizard man from lepar island, not just crusty elbows). It's a protein that I have to inject twice a week since taking it orally would end with my body digesting the meds. I could see genetically engineering a bacteria that could live in the intestine and produce the medicine. That would be awesome.

  • For the benefit of the slashdot crowd (Score:5, Informative)

    by soren.harward ( 1153 ) on Thursday September 22, 2005 @10:25AM (#13621265) Homepage

    Since protein engineering is my field [upenn.edu] of study, for the benefit of the /. crowd (and my karma) I'll fill in the gaping holes left in the New Scientist article, and give you a little more background on the Nature paper. Because the writeup on /. is a perfect example of "scientific telephone": a semi-interesting result gets written up into a paper, which once it's been through several layers of editors suddenly seems like a major breakthrough.

    The Nature paper isn't a breakthrough. It's not even really a major advance. Scientists in my field have been creating artificial proteins for five to ten years now. And yes, even some of them designed completely from scratch (though they're really simple; nothing as complex as, say, ATP synthase) instead of just taking a known fold pattern, known as a "motif." The "WW domain" (domain, in protein parlance, is a small, independent structure within a much larger protein---think of it like a module within the kernel or Apache) is a common fold in hundreds of different proteins. Basically, they analyzed the sequences of all of these WW domains, and figured out which positions were meaningful. It's kinda like reading through some code in a programming language you don't know, and figuring out which lines are comments and which lines are actual compilable code. This group found that the number of interesting positions is small, that they could identify them just from the amino acide sequence instead of having to mess with the whole complicated 3D structure of the domain, and that if they put together a protein with the meaningful amino acids intact and the non-meaningful positions randomized, then in many cases they could still get a pretty decent protein (in terms of structural similarity to the "natural" protein) out of it. Most of the paper is devoted to showing via various methods that they did get a pretty decent protein.

    So what does this mean for me, assuming that this paper is absolutely correct (which I admit is a little hard for me to determine with one quick reading, given that I'm just a first-year grad student)? It means that the number of meaningful amino acids in a protein (at least in terms of overall structure) is pretty low, and that they can be identified without knowing what the full 3D structure is. This is good, because for a lot of proteins, the 3D structure is difficult to get. However, they picked an easy target: a small domain where there are over 100 unique sequences known. We'll see how well this method holds up with longer domains and fewer unique sequences. The S/N ratio won't be nearly as good.

  • The real breakthru here is reverse-engineering proteins to get their "designer genes". That's one of the goals of giant computational undertakings like Folding@Home. Now every Folding team will be getting our discount coupons on the products of that "free" research we did for the drug companies, right?
  • Let's hope they figure out with complete certainty what the rules are for making prions -- and then nobody does it.

    Otherwise we've got an Ice-9 problem.

    I hope the folks making artificial proteins have thought long and hard about proteins that make themselves -- and what defines them. Meanwhile don't lick your fingers, kids.

    http://www.newscientist.com/channel/health/mg18725 144.300 [newscientist.com]

    'Mad ewes' give birth to BSE lambs
    * 27 August 2005
    * Debora MacKenzie

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