Create a Protein with Your Mind

Why don’t you think purifying selection is the most likely cause of extreme preservation? Especially with a mission critical cellular function?

I do think purifying selection is the cause of preservation. But it doesn’t have to be preservation against lethal mutations, just mutations with lower fitness. A mutation doesn’t have to cause instant death to be selected against, it just needs to cause lower reproductive success.

That means other mutants we don’t normally see in any population might strictly be viable in the sense that an organism with that mutation could still be able to survive and reproduce, it just has significantly fewer offspring than organisms without that mutation. In that sense, should the mutation arise, it will be outcompeted and so fail to fix in the population.

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Are you claiming splicing errors lead to fewer offspring? How would this process work?

Do I now have to explain to you how genes contribute to organismal fitness? Some human Prp8 mutations cause blindness. Do I have to explain how vision relates to your ability to survive, find mates, and produce offspring?

Didn’t I explain this exact same thing to you before on this very website? I seem to recall something about that. Let me see…

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Oh yeah, it’s here: Chance and Providence (reprised) - #139 by Rumraket

Here’s what I wrote there:

Simply looking up the Prp8 protein on wikipedia will tell you there are human Prp8 mutants living among us, and some of these apparently negatively affect vision, leading some of them eventually go blind in adulthood. That’s strongly deleterious, which would explain why such mutants haven’t fixed in the population. But they’re clearly not lethal, since there are people running around with them.

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It’s not a straw man. “Preservation data” is nothing more than using BLAST, and the sequence that comes out of it is a single, solitary sequence.

That is, as far as I know, a whole lot different from 10^100.

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Its multiple sequence samples from the same protein in different animals which are compared. The sequences have some differences most of the time.

It’s clear to everyone else they do understand your silly “argument” and it’s just you who refuses to admit it’s been completely falsified too many times to count.

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Good for them :slight_smile:

Bad for you. :slight_smile:

How can you assess them without the evidence, Bill?

An estimate derived from aggressive ignorance of the evidence is rarely a good one.

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You have zero evidentiary basis for your claim. Just because you wish it was true doesn’t make it so.

Are you claiming that splicing is very accurate? That it doesn’t produce lots of useless products? That would be funny.

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It’s a useless metric, derived only for polemic reasons.

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Agreed.

Yes. That line of argument ran off the rails long ago and headed deep into the mountain wilderness. It would take a large-scale search-and-rescue party to find the cave where it sought refuge. (In other words, probably at a weekend conference marketed to science-skeptical Christians. I still get invited to them now and then.)

Meanwhile, I must admit that I did a double-take when I first saw the thread title, “Create a Protein with Your Mind.” I wondered to myself, “Has telekinetic biochemistry truly come that far?”

If telekinesis has become that useful, who needs CRISPR?

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Sorry I missed your question. By “we” I meant the scientific community. Designer transcription factors is one. Anything that might involve wanting to target a specific part of the DNA is another. This would involve genetic therapeutic drug targets.

Some of the paper on this are old, but the tools still float around on the net:
Papers:

Tools: to design zinc finger proteins:
https://www.scripps.edu/barbas/zfdesign/zfdesignhome.php

You are probably going to need high-resolution structures of the ZFP bound to DNA to do anything. If bound water is anywhere in the DNA-protein interaction, I doubt that AI is going to be of much use.

That may explain some of the problems with present AI tools. Anyway I played with one of the tools and it didn’t work so well. I typed in a known zinc finger array and it spewed out what it thought was the predicted DNA it binds to. The AI tool predicted the array would bind to a totally different sequence than what experiment showed it actually binds to. Current AI theory was falsified by experiment!

Anyway, here is a graphic, but don’t take the metaphor of keys too far since a zinc-finger is more like a lock. It was one I presented to biology faculty and deans this year:

Another slide from my zinc-finger/promiscuous domain presentation: