Monday, September 26, 2011

The Protein Engineer

 
Two former undergraduate students of mine have started a blog called The Protein Engineer.
A blog started by two graduate students, 11000 kilometres apart, on a quest to discover, or otherwise invent, the holy grail of bioengineering: rational protein design.

Our blog consists of weekly reviews of important papers within the cutting edge field that is an amalgam of theoretical and experimental biology, fused with a heavy dose of computational engineering. At the same time, our posts are accessible to even the keen undergraduate in science or engineering.

In nature, new proteins are created by means of mutations and recombination in the DNA, a process that can take thousands of years, and only then, whose purpose serves only strengthen the fitness of the host organism, a purpose often ill-suited for industry or medicine. Protein engineering aspires to create new proteins within a year or less, using powerful computational and experimental techniques such as simulation and directed evolution to create custom-tailored proteins designed especially for industry or medicine.

But more importantly, we hope to fascinate our readers with the immense possibilities of protein engineering. So that perhaps one day, you too, will become a proteneer.


23 comments :

  1. That's great! Protein engineering and artificial selection demonstrate the power of intelligent design compared to the inefficacy of evolution by natural selection.

    Hopefully, your own students will pave the way for the gradual acceptance of intelligent design in the scientific community. You must be doing something right, Larry.

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  2. Atheistoclast says,

    That's great! Protein engineering and artificial selection demonstrate the power of intelligent design compared to the inefficacy of evolution by natural selection.

    Hopefully, your own students will pave the way for the gradual acceptance of intelligent design in the scientific community. You must be doing something right, Larry.


    Thanks. I teach introductory biochemistry from an evolutionary perspective. Students learn that most of what we see at the molecular level is the product of haphazard "tinkering" coupled to contingency and accident.

    They learn that there are very few enzymes or pathways that look well-designed or even perfectly adapted. By the time students absorb this reality of nature, they have come to understand that any competent biochemist—even an undergraduate—could do a better job of designing a cell.

    They will also have learned that biochemistry provides absolutely no evidence for an intelligent, omnipotent, omniscient God.

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  3. My understanding (2nd year organic chemistry convinced me that my future was in computers) is that earlier versions of "modern" enzymes were sloppy in the sense that they would catalyze a broader range of reactions, albeit less efficiently.

    Over time enzymes evolved to become much more specific as to which reactions they would catalyze and became corresponding more efficient.

    This appears like natural selection at work, where random changes to enzymes that resulted in a more efficient/faster reaction had a greater benefit to the organism than the cost of catalyzing fewer reactions.

    If this were the case one would expect to see molecules that are the result of generations of contingent change and would be the antithesis of design.

    What would a "designed" enzyme look like ?

    Is there some sort of metric of "designedness" that can be applied to protiens ?

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  4. Atheistoclast: I use directed evolution to design my proteins, a method that works entirely due to the power of natural selection.

    (Yutong uses rational design, and on this issue we've agreed to disagree)

    Make no mistake, nobody in the protein design community argues that natural systems were intelligently designed.

    Steve: You're right that ancestral enzymes had broader substrate specificity, presumably at the cost of catalytic activity.

    In the lab we've found that it is rather difficult to evolve proteins to perform their natural function significantly better. It's a fair bit easier to evolve a side activity. We attribute this to natural evolution finding local fitness maxima in protein sequence space.

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  5. Larry,

    Have you ever heard of "directed evolution" and "induced mutagenesis" before. The fact is that the most profoundly important changes in enzymes are due to human (intelligent) intervention in Nature. Devin is wrong. "Fitter enzymes" may be produced that work in vitro but the process that makes them so fit is not undirected.

    There are natural constraints to natural evolution that artificial selection can ignore if necessary.

    Btw, if you teach them that the architecture and operation of the cell is explicable in terms of just physics and chemistry....I really should enroll in your class.I have to hear this.

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  6. I suggest you keep reading my blog then Atheistoclast, you clearly have a lot to learn.

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  7. > Dr. Moran: ... they have come to understand that any competent biochemist—even an undergraduate—could do a better job of designing a cell.

    I do wonder then, why they don't do it! I'm thinking the journal Cell does not yet publish cell designs for some reason.

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  8. "Fitter enzymes" may be produced that work in vitro but the process that makes them so fit is not undirected.

    Correct. And the "directing process" is called Natural Selection over a few billion years.

    Stop the straw-man attacks. Evolution has a undirected component (genetic drift) and a directed component (selection). This does not require an intelligence pulling the string.

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  9. Devin,

    Please tell me how your work in directed evolution in a lab mimicks in vivo undirected evolution. I'd really like to hear this. Maybe you should read this paper:

    The intelligent design of evolution

    What part of the title of the article do you not understand?

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  10. lee_merrill said...

    I do wonder then, why they don't do it! I'm thinking the journal Cell does not yet publish cell designs for some reason.

    Possibly because so many resources are diverted to battling creationist idiots.

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  11. @Atheistoclast I really should enroll in your class.

    As has been apparent from the contents of your posts.

    The sooner the better.

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  12. @Atheistoclast,

    Read up on the in vitro evolution of Ribosymes and DNAzymes. Researchers are generating catalytic activity from random pools or RNA or DNA oligonucleotide. The method involves running the pool through some sort of column to bind a substrate or a mimic of a transition state of a chemical reaction. Binding nucleotides are amplified under error-prone conditions to produce diversity around the ones that seem to work. Through directed evolution, there are enzymes that never existed before, made of RNA and DNA.

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  13. Devin,

    I would suggest you not to answer to anything by this Atheistoclast. The likes of this guy don't care about your answers. They think they know much better than the people doing the actual experiments (example, he thinks he knows better than you). If a title or a little isolated sentence seems to sound even if slightly as what they want to "promote" they will use it. See how he wants to sell you a tittle in a paper, instead of he learning what the articles actually say, and the broader picture from several examples and experiments, like your accumulated experience, which he could not care less about because he cannot quote-mine. He needs one article from you, one where you mention "intelligence" or "directed," or whatever else he can use to lie about your results and promote his crap.

    Note also that he will deny that anything in the lab demonstrates evolution. He could not care less that the experiments involve random variation, and selection. No matter how carefully an experiment is done, he will say it "demonstrates intelligent design." The likes of Atheistoclast are called IDiots for a reason. To them, if you even slightly touched any of the reactants, you are using intelligence, and thus you demonstrate intelligent design. That's the nature of IDiocy. They know better than actual scientists. Then, evolution is false because you can't do experiments in the lab, but if you can do experiments in the lab, then you demonstrate intelligent design. Win-win situation, no matter how obviously dishonest the IDiots have to be. What is truly sad about this is that their clientele does not notice this problem. They will not note it even after reading my following paragraph:

    Of course, we know that planets move because of intelligent orbitation. Every experiment, every satellite launched into space, was touched by a human, thus demonstrating that natural gravitation is completely made up. All those experiments demonstrated intelligent orbitation. God is moving those planets and gravitation was invented to deny this obvious fact. Planets would to be able to move, let alone in ellipses, without an intelligent being moving them. Show me a single thing moving in ellipses by chance! So there!

    Best! (Nice and interesting blog by the way).

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  14. Yes. Atheistoclast isn't here to try and get a better understanding of the science. He thinks he's got it figured out, and he's only here to fly the creobot flag on behalf of his percieved creator.

    I'm afraid the issue is that no intellectual argument can sway Atheistoclast. He is blinded by a deep sense of religious piety into supposing that he is the intended creation of a magic mind that loves him, and with no purpose other than the glorification of and submission to this mind. He has put on his armor of god and come to do battle. His intentions are exquisitely revealed in his choise of name. He must break the atheists. Theism is, bizarrely, comforting to Atheistoclast, who fears having to face up to his personal freedom, desires and especially his mortality. That is how I have come to understand atheistoclast all too well over the last couple of years. He will never be persuaded with reason and evidence. He has no interest in the actual science. He has identified with the supernaturalist orthodoxy within religion and cherish it like it was something sacred and inviolable. He regards anything other than the glorification of god as sinful and degenerative. Nature can be reduced to the wishes and fleeting whims and intentions of the All-Wise power. This world view has no joy, no life or any place for the pursuit of answers to questions about the mysteries and wonders of the natural world. Indeed, anything that even remotely smells like a gap in our knowledge is hailed as the quintessential proof of god and an utter falsification of naturalism, regardless of its scientific merit. If tomorrow someone argues there is unsolved questions in abiogenesis, evolution or the origins of the universe, he will seize upon it like manna from heaven. Therefore, atheistoclast has essentially found refuge in gap-theology and it is a source of joy and comfort to him as much as his faith in God is. Even though I find it appalling and shallow, he sees it as wonderful. So even though he is committed to destroying atheism through emotional outbursts and willful misrepresentations, the best approach may be to appeal to his psychological and pathological condition which is surrounded by some very twisted and perverse logic.

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  15. Negative Entropy says: To them, if you even slightly touched any of the reactants, you are using intelligence, and thus you demonstrate intelligent design.

    He'll go further, it's much worse than that. Using Lenski's evolution experiments as examples, where the bacteria adapted to life in a single, static environment, they ended up with a number of deletions in genes they no longer needed. Atheistoclast will then go on to argue that this proves evolution is only degenerative, can only destroy or delete genetic information, or at best, conserve extant genes. He simply flat out denies the capacity for selection on random variation to produce any form of novelty. He'll argue that enzymes can't change their function through evolution with fancy phrases like "noone ever saw a cyclin evolve into an integrin", but that they only change into related functions, like esterases into other, closely related hydrolases. Anything he needs to convince himself that he isn't a great ape.

    Don't make the mistake of thinking he's unintelligent. Just profoundly, deeply delusional and emotionally comitted to his presupposition. The God-trooper is here to fight and break the atheist.

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  16. @The Other Jim

    That's great stuff. I wish the researchers all the best in their intelligent efforts at directed evolution in producing enzymes that Nature could never possibly produce.

    Btw, evolution by natural selection works in vivo and not in vitro. Just in case you didn't know.

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  17. Re Devin

    I agree with Mr. Negative Entropy that it is a total waste of time to get into a discussion with clowns like Atheistoclast,k whose mind, like all creationists, is made up and any contrary facts are irrelevant. See Richard Dawkins' comment on Kurt Wise.

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  18. I would suggest you not to answer to anything by this Atheistoclast.

    Though I agree with you that we will never get him to waver from his stance, blog posts are read by a more general public who end up at these sites via google, at a much later date. To leave the creationist nonsense unchallenged may make is seem like a respectable position to those who visit the comments section after the discussion has ended.

    At least that's what motivates me to post in response sometimes.

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  19. Atheistoclast said...

    Btw, evolution by natural selection works in vivo and not in vitro. Just in case you didn't know.


    This claim is demonstrably incorrect.

    Et al. & Lenski.
    doi:10.1186/1471-2148-10-11
    doi:10.1186/1471-2148-9-302

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  20. I am not really a fundamentalist or creationist because I have no problem with an Old Earth and a broad (though maybe not universal) common descent. However, I reject natural selection as a "creative force" ,as there is no evidence for this, and I believe life is sustained by a "vital principle". I seek the middle path, away from the extremists on both sides. The truth lies in the middle. I may upset people but I also make them question their assumptions and prejudices.

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  21. Hey The other Jim,

    Agreed that onlookers might benefit from seeing some answers. But my reason not to answer to Atheistoclast (though I used to), is not that he will not be waved from his stance. The problem is that he will just play with words and sell titles and misquotes. There is a point where the stupidity of the likes of this kind of people just have to be shown for what it is, rather than try and first, pretend that these people are actually asking a question (they are not, they are playing rhetorical tricks), and second, translate whatever nonsense they sprout, into a reasonable question that they actually did not make. They will use whatever honest effort you make to talk to them into a new set of rhetorical crap. Just see what this imbecile did now. He just bolded the words "intelligent" and "directed" in his comment as if that was a triumphant card. Proud of my signalling his utter and unbelievable level of stupidity.

    But sure, some actual answers will be useful. But if you are going to engage, just make sure you are answering what is actually there, rather than assume honesty and answer what you think they asked.

    Let's see what he will do with your references to Lenski now ...

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  22. Wow. I'm giving seminar to my department in a couple weeks on this very topic, specifically discussing recent papers from David Baker's lab. This site is going to be extremely helpful! Thanks so much!

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  23. awesome - I worked on the FoldIt! project in the Baker Lab back in 2008.

    I hope your talk goes well.

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