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Thread: Designer enzymes

  1. #1
    tWebber lee_merrill's Avatar
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    Designer enzymes

    Source: Marcos Eberlin, from the book "Foresight"

    The scientists and the media are excited about the possibilities of bringing intelligence to bear on the problem of enzyme design. Working from the assumption that enzymes are the product of evolutionary processes, Baker says, “There’s a lot of things that nature has come up with just by randomly bumbling around.” And he adds, “As we understand more and more of the basic principles, we ought to be able to do far better.”1 We’ll see. It’s an interesting reverse test of intelligent design, don’t you think?2

    © Copyright Original Source


    I think so! Humans ought to be able to improve on bumbling nature, if that is how enzymes came to be.

    Blessings,
    Lee

    1. Referenced here.
    2. Referenced here.
    "What I pray of you is, to keep your eye upon Him, for that is everything. Do you say, 'How am I to keep my eye on Him?' I reply, keep your eye off everything else, and you will soon see Him. All depends on the eye of faith being kept on Him. How simple it is!" (J.B. Stoney)

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    tWebber shunyadragon's Avatar
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    Quote Originally Posted by lee_merrill View Post
    Source: Marcos Eberlin, from the book "Foresight"

    The scientists and the media are excited about the possibilities of bringing intelligence to bear on the problem of enzyme design. Working from the assumption that enzymes are the product of evolutionary processes, Baker says, “There’s a lot of things that nature has come up with just by randomly bumbling around.” And he adds, “As we understand more and more of the basic principles, we ought to be able to do far better.”1 We’ll see. It’s an interesting reverse test of intelligent design, don’t you think?2

    © Copyright Original Source


    I think so! Humans ought to be able to improve on bumbling nature, if that is how enzymes came to be.

    Blessings,
    Lee

    1. Referenced here.
    2. Referenced here.
    Ooooops!!! First hint of a serious ID foupa here: “There’s a lot of things that nature has come up with just by randomly bumbling around.”

    Problem as usual with the layman misuse of randomness. Nature does not 'randomly bumble around.' What a silly anthropomorphic explanation for science.

    Maybe in the future we will have enzymes running around in designer suits.
    Last edited by shunyadragon; 06-11-2019 at 07:08 PM.
    Glendower: I can call spirits from the vasty deep.
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    tWebber TheLurch's Avatar
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    Quote Originally Posted by lee_merrill View Post
    I think so! Humans ought to be able to improve on bumbling nature, if that is how enzymes came to be.
    Here in reality, "bumbling nature" has had billions of years to explore potential optimizations of most key enzymes. For the most part, if better performance can be had, nature would already have it. There are some notable exceptions to this, like RUBISCO, but they're notable because they're so rare.

    That said, I also see potential here, but of a more limited sort: we have to examine the underlying biology to find useful cases that evolution wouldn't have optimized. This would include things like:
    — Enzymes that are on biochemical pathways where some other reaction is limiting, and therefore provide no advantage by operating more efficiently.
    — Enzymes that catalyze a reaction under conditions that aren't useful to us could be optimized for operation in conditions that are (different solvent, pH, etc.).
    — Enzymes that normally work as part of one pathway, but we'd like to have working as part of a different one.
    — Things that the cell normally tightly controls for metabolic balance, but we want operating at full speed all the time.
    — Almost certainly others that I can't think of right now.

    The unfortunate fact of the matter for Lee is that, if you follow the literature in this field, you'll find that, when faced with wanting to do this, most researchers have simply found it best to stick an enzyme into the context they want it to work in, and put it through multiple rounds of random mutagenesis and evolutionary selection*. There have been cases of intentional design, but they're the minority. In a number of cases, design was tried and failed, forcing researchers to turn to evolutionary approaches.

    Where I think design will ultimately matter is when we start doing more with unnatural amino acids. These can have a chemistry that can be quite distinct from anything that existing enzymes have to work with, and therefore probably can't be dropped into an existing enzyme with good results.

    *Edited to add: there are reasons for this i can go into if people are interested.
    Last edited by TheLurch; 06-12-2019 at 09:19 AM.
    "Any sufficiently advanced stupidity is indistinguishable from trolling."

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    tWebber lee_merrill's Avatar
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    Well, the "bumbling" quote was from David Baker, an evolutionist. And if as the Lurch said, intentional design doesn't work very well, then it will be interesting to see when and if this field flourishes and surpasses by far what nature does. If not, then there's evidence for design!

    Blessings,
    Lee
    "What I pray of you is, to keep your eye upon Him, for that is everything. Do you say, 'How am I to keep my eye on Him?' I reply, keep your eye off everything else, and you will soon see Him. All depends on the eye of faith being kept on Him. How simple it is!" (J.B. Stoney)

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    tWebber TheLurch's Avatar
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    Quote Originally Posted by lee_merrill View Post
    Well, the "bumbling" quote was from David Baker, an evolutionist. And if as the Lurch said, intentional design doesn't work very well, then it will be interesting to see when and if this field flourishes and surpasses by far what nature does. If not, then there's evidence for design!
    Wait, as written, this says that if design fails to surpass evolution, then it's evidence for design. Is that really what you meant?
    "Any sufficiently advanced stupidity is indistinguishable from trolling."

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    tWebber lee_merrill's Avatar
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    Quote Originally Posted by TheLurch View Post
    Wait, as written, this says that if design fails to surpass evolution, then it's evidence for design. Is that really what you meant?
    Yes, we should be able to beat such a process. "It’s an interesting reverse test of intelligent design, don’t you think?"

    Blessings,
    Lee
    "What I pray of you is, to keep your eye upon Him, for that is everything. Do you say, 'How am I to keep my eye on Him?' I reply, keep your eye off everything else, and you will soon see Him. All depends on the eye of faith being kept on Him. How simple it is!" (J.B. Stoney)

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    tWebber TheLurch's Avatar
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    Quote Originally Posted by lee_merrill View Post
    Yes, we should be able to beat such a process. "It’s an interesting reverse test of intelligent design, don’t you think?"
    That's the exact opposite of what i said, and the opposite of what you said earlier.

    Would you at least pay the rest of us the respect of paying attention to your own arguments?
    "Any sufficiently advanced stupidity is indistinguishable from trolling."

  8. Amen Seeker, shunyadragon, Roy amen'd this post.
  9. #8
    tWebber shunyadragon's Avatar
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    Quote Originally Posted by lee_merrill View Post
    Well, the "bumbling" quote was from David Baker,

    Blessings,
    Lee
    I most definitely consider you misrepresenting Dr. Baker. You need to cite him more fully and completely.
    Glendower: I can call spirits from the vasty deep.
    Hotspur: Why, so can I, or so can any man;
    But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

    go with the flow the river knows . . .

    Frank

    I do not know, therefore everything is in pencil.

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    tWebber shunyadragon's Avatar
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    Quote Originally Posted by shunyadragon View Post
    I most definitely consider you misrepresenting Dr. Baker. You need to cite him more fully and completely.
    The problem with the quote from Dr. Baker, when taken into context of the 'whole' article is that it is a frivolous rhetorical devise statement, and when Marcos Eberlin uses the quote he takes it seriously how nature actually works from the scientific perspective.

    If you read the whole article by Dr. Baker you will find the article is definite scientific perspective of evolution, and than read Marcos Eberlin his work is an 'Intelligent Design' argument in total contradiction of the science of Dr. Baker.

    Context, context and context.
    Glendower: I can call spirits from the vasty deep.
    Hotspur: Why, so can I, or so can any man;
    But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

    go with the flow the river knows . . .

    Frank

    I do not know, therefore everything is in pencil.

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    tWebber TheLurch's Avatar
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    Got a bit of a break at work, so thought i'd discuss why designing enzymes without using evolution is really, really difficult.

    The first issue is the number of problems you've got to solve at once. You may think it's just a matter of chemistry - throw in a positive charge and the reaction should go faster. But there are also structural issues. Maybe the positively charged amino acids are too big to fit into the active site; maybe there are other positive charges nearby that would be repelled by it; etc.

    But the big sticking point is that you're also solving a protein-folding problem. Proteins start to fold up as they're being made, which means that any changes you make can potentially start interacting with parts of the protein they'd otherwise be shielded from in a mature protein. So your positive charge might end up sticking to a negative charge somewhere else in the protein that would be inaccessible when the entire protein was intact and folded properly. So, to really understand what changes will be tolerated, we need to fully understand protein folding - a problem researchers have been struggling with for decades.

    These aren't impossible barriers, but they mean you generally have to try a number of potential changes in order to be reasonably certain you'll find one that works. And that bumps up against the next problem: it's time consuming to engineer specific changes. You have to manipulate the DNA sequences, get them back into the original gene, get the gene into an organism, check by DNA sequencing that no errors were introduced during the process...

    Contrast this with an evolutionary approach. Evolution solves for activity, structural concerns, and folding simultaneously. It tries options we wouldn't necessarily think of. If done for multiple rounds, it provides the possibility of adding mutations that compensate for any problematic effects of the desired changes. A single Petri dish can examine far more changes than can ever reasonably be tested directly. And, given the hassle of engineering changes above, it's possible to do multiple rounds of selection in the same time it would take to engineer and test a single change.

    This doesn't mean it's perfect for everything. There's cases where it's hard to set up any kind of selection for a specific activity, which makes it impossible to evolve for better performance of that activity. Outside those cases, however, it's very practical, and far more likely to deliver an improved version of an enzyme.
    "Any sufficiently advanced stupidity is indistinguishable from trolling."

  12. Amen shunyadragon, lee_merrill amen'd this post.

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