Marty's testable ID hypothesis

Continuing the discussion from Dembski Responds to Rosenhouse:

This is how I would expect intelligently designed protein complexes to work, Marty. It is not how I would expect ones that evolved by the known mechanisms of variation, selection, and drift to work.

Let’s check out whether your hypothesis (which you presented as fact) applies to muscle myosin, which catalyzes the hydrolysis of ATP.

Are you up for that?


Marty would like you to know that he is not “up for that.”


Of course not! That would be using the scientific method.


Changed my mind here, since all your bromance buddies have “hearted” the query, and since to the ignorant, ignoring people is tantamount to accepting their thesis. As you assert with your arrogant follow-on.

So explain what’s wrong with my statement as it regards myosin. You are suggesting that the binding site is NOT at a “right” location for the protein to have meaningful function.

Marty, there’s absolutely nothing arrogant about my pointing out the falsehood of your claim. I’m an expert, you are not. Do you dispute that?

I’ve found that arrogant people, after being questioned on a claim, attempt to shift the evidentiary burden.

I’ve also found that arrogant people move goalposts and use the straw man fallacy often, even stacking two fallacies! Why did quaternary structure and catalytic activity disappear from your claim?

I’m pointing out that the falsehood of your unsupported, global claim is far more fundamental (and revealing) than that.

When we design machines, we control them by turning them on. You have unwittingly affirmed that this is an integral part of your design hypothesis by misrepresenting the way that things work in real time. As a scientist who constantly questions my own assumptions, it is easy to see that your false claim is merely a prediction of your design hypothesis.

Muscle myosins are hexamers. The heavy chains dimerize by a very long, alpha-helical coiled-coil “tail”. We can remove that dimerization (a major part of its quaternary structure) by cleavage with a protease. Your hypothesis very clearly predicts that no catalytic activity would remain.

We can remove the two light chains from the remaining trimeric “S1” fragments that no longer dimerize, completely destroying ALL quaternary structure. Your hypothesis very clearly predicts that no catalytic activity would remain.

Evolution is more constrained than design, so it tends to build complex mechanisms differently.

Now, how about providing 5 cases (not hearsay, but evidence) that you know to be consistent with your global design hypothesis:


Are you suggesting that someone who is right cannot be arrogant? Seriously? In addition the authority you attempt to claim for yourself, putting on your lab coat like someone putting on a clerical collar, does not impress. Plenty of highly educated people are arrogant, self-important, socially inept, hawking personal agendas, and wrong. You should let your game do the talking. So first, sorry to say it, but get over yourself and stick with the subject.

In my initial reply to Dan refusing your offer here, I said it was because you are frequently abusive and nitpicking (if I recall correctly). Your post is a great example so first I will engage with that context. I knew you had cherry picked an example and were planning to attempt to show your superior brilliance at my expense. I didn’t really want to play this game of yours partly because it simply takes too long, and partly because I didn’t want to have to say most of this. I hate writing tomes. But I guess I have to.

Using the word “false” repeatedly regarding my statement is meaningless. It does not make it so, and I can find no reason other than you making yourself feel superior in your own eyes. Just get to the point.

Most important, rather than even considering in what way my statement might be true, you have read into my statement a global absolute of epic proportions, a new “scientific design hypothesis” or “testable ID hypothesis.” Why? Apparently so you can attempt to show it false? But what utter BS you have claimed I said.

You show no interest in clarifying what I meant or where my statement might be true or have boundaries, but have started this thread with no other purpose than to try humiliate me and cower me into submission. The most important falsehood here is how you have misread one simple sentence to hawk your ID-hating agenda. You have assumed I am an idiot and seem to be salivating at trying to show me so. What kind of person does this?

What?! It didn’t. In English, my query is shorthand for what was said before, but negated. You accuse me of stacking fallacies when you fail to understand normal English usage. Seems this thread is all about that.

I asked you to clarify your OP claim and show me how my statement is wrong. If I don’t know what you think is wrong with it, how on earth am I going to answer? You say I’m trying to “shift the evidentiary burden” or “moving the goalposts” or “straw man.” But don’t you think I would like to understand what the heck you’re talking about before I reply? Well maybe not, since apparently you don’t care to understand what I meant before you start a new thread with deep disdain using your hopeless misreading. And apparently only you get to ask the questions, and others are not allowed to? How convenient, or manipulative, depending on which side it is seen from!

Most people might first try to see in what way my statement could be understood so that it makes sense. If you are unable to see any truth in it, then either you are not an expert or the axe you are grinding is so important to you that you cannot see past it. Read it again, and ask yourself, “In what ways might this be true?”

Now I will talk about my very simple sentence in the original post and engage with the science. What percentage of random bound polypeptide complexes will produce meaningful catalytic activity? We don’t know, of course, but it’s not a lot, is it. Maybe we can say, “10 to the minus something double digits.” Rare. If someone has a better number, please provide a reference.

OK, take the DNA in a cell, and in every gene whose product is part of a protein complex, move every binding site maybe ten amino acids one way or the other. Reverse the order of some of them. Many subunits would still find each other, but would the resulting complex have any meaningful function? If it affected the active site, that most likely would no longer work. I’m thinking your example might be an exception in this category, an unaffected active site. It’s always plausible some other catalytic activity might be enabled, but again, probably not.

Then let’s take a specific example. Move all the subunit binding sites on ATP Synthase to the ends of the subunits. Will the complex have any meaningful activity? Probably not.

Are there some scientific details in these paragraphs that could be improved? Probably. Nitpickers in that regard are not welcome here, however additional meaningful insights are welcome. So don’t the binding sites on each subunit of a protein complex need to be in a “right” location? There may be other “right” locations, and possibly other activity, but clearly “any” location will not do.

So fundamentally, my sentence is true. And that has nothing to do with design arguments or “intelligently designed complexes”, or even evolution. It has to do with protein complexes, their structure, and their catalytic activity. These are deeply interrelated, and binding site locations matter.

Relating back to the original discussion on antibodies, that is orders of magnitude less so with antibodies. That was my point.

These are implied in my sentence. Not some grandiose ID hypothesis which you chose to impose on it. But I’d have been glad to tell you what I meant if you had just started with the assumption that I’m not an idiot and had asked for simple clarity.

In my opinion, if you have an interest in truly helping people understand science, you need to work on your approach. Make sure you understand first what someone is really saying.

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Shame about your chessboard. This should help:

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Nope. I described a specific case. Why are you pretending that I made some sort of global claim?

The evidence seems not to matter to you either. Why is that?

I am, and note that you are doing anything but.

Is this an example of you letting your game doing the talking?

Really? You accuse me of cherry-picking, then do not offer a single case that contradicts it? Fascinating.

You could, instead, engage with the scientific method and the cryptic hypothesis you offered, but you’re ranting.

Because it’s there, Marty. You built in a false assumption that comes from your design hypothesis–that (try to read carefully here) protein interactions (quaternary structure) regulate catalytic activity POSITIVELY.

Your hypothesis is that these interactions are required to turn catalysis on. It’s just wrong, so it falsifies your tacit design hypothesis. That’s how we humans would design life, but it is rarely available to evolutionary mechanisms. The selective advantage conferred by a new catalytic activity (or range of activities) evolves first, then it is regulated, typically negatively.

Can you see that “negatively” is the polar opposite of “POSITIVELY”?

I quoted what you said and responded directly to it.

Or maybe I just don’t want people to spread false claims, based on false assumptions, about how biology actually works in real time.

You haven’t shown how I misread it, Marty.

It did:

Then when I challenged it, you falsely claimed that I was misrepresenting it, while removing the specifics:

I didn’t suggest anything at all about right or wrong locations of binding sites. I challenged something much more fundamental and revealing: your false claim about how those interactions regulate function:

It was not even close to what I wrote. It was a classic straw man.

And I did, with one of biology’s most-studied examples, myosin.

Your false claim:

For myosin, eliminating all quaternary structure preserves and enhances catalytic activity. It’s the sort of regulation we expect and observe routinely with the iterative mechanisms of evolution, but not with design.

I did. I don’t see how you could miss my point:

Do you see anything about locations of binding sites in there?

That’s not arrogant at all, right, Marty?

None, as a global statement.

That’s irrelevant to your claim. The falsehood of it is in what quaternary structure does.

Irrelevant. The falsehood of your claim is in what you claimed that binding does to catalytic activity.

I’m thinking that your Culture Warrior mentality is preventing you from reading what I wrote.

We can go to higher-order muscle structure and it gets even worse for your claim. Myosins do not simply transduce ATP hydrolysis to force generation in the much more direct way that your car burns gasoline to turn the crankshaft and wheels.

Can you name even a single protein complex in which the catalytic activity is shared between proteins, in that they have to be interacting for catalysis to occur?

Again, exceptions would be cases in which the interactions are required for catalytic activity. My point is that because you are assuming that these were designed, you are assuming that they are designed in the way that you might design them–to turn on. Evolution, as a rule (although there are certain to be rare exceptions) doesn’t have that option.

Fundamentally, your sentence is false.

I didn’t impose anything. You made the assumption that quaternary structure is required for enzymatic activity. It has nothing to do with wrong or right binding sites or their locations. Can you name a single case?


Leroy Anderson was a genius. Just sayin’.

It’s not really an example, it’s an extreme case showing the most that evolution can do, but let’s.

The test is much simpler and analogous to that for the myosin ATPase. Does the beta subunit still have catalytic activity in the absence of the other subunits?

Contrast that with what actual intelligent design can produce:

This review also includes citations for split enzymes. Humans have executed this design strategy many times, but nature (AFAIK) does not exploit this obvious, positive regulatory mechanism. Even if nature managed to do so rarely, the difference remains vast. Why?

Even with applying your misunderstanding of my original sentence, I don’t see how this applies. Fluorescence is not a catalytic activity.

I didn’t misunderstand your original sentence. You clearly stated that quaternary structure is required for catalytic activity. That’s a mechanistic design hypothesis that makes clear empirical predictions.

That’s true for human-designed split proteins that are routinely used as sensors, but AFAIK it’s beyond the real edge of evolution, not reachable by an iterative process.

That’s why I wrote:

Did you miss that because you are unaware that enzymes have catalytic activity?

Apparently, you didn’t click on the link, because an enzyme, ribonuclease, is described in section 1.1.

In section 1.3:

The original example of a conditional split protein complementation system was reported by Johnsson & Varshavsky (50), who demonstrated that ubiquitin fragments only reassembled into an active protease tag when fused to two interacting proteins (a leucine zipper homodimer). This pivotal split ubiquitin system laid the foundation for all future protein-fragment complementation assays (PCAs) that link the function of a split reporter protein to a specific protein–protein interaction (PPI) (Figure 1). Conceptually, any protein whose activity results in a clear and measurable readout can act as the reporter in a PCA. To date, many proteins, such as ubiquitin (50), β-galactosidase (118), dihydrofolate reductase (104), β-lactamase (36), firefly luciferase (81), TEV protease (152), thymidine kinase (84), Cas9 (160), horseradish peroxidase (83), RNA polymerase (106), and aminoacyl tRNA synthetase (134), have been engineered as split PCA reporters to detect both transient and irreversible PPIs. The types of readouts for these assays include fluorescence, bioluminescence, cell survival, gene transcription, protein translation, positron emission, genome editing, and electron microscopy. Since this review focuses on split fluorescent proteins (FPs) and their numerous and often overlooked applications, we refer the interested reader to earlier, thorough reviews for more details about the properties and scope of split nonfluorescent proteins (85, 89, 90, 127, 153, 154).

In case you did read it and are unaware, that “-ase” suffix refers to catalytic activity.

Humans routinely design split proteins for which quaternary structure is essential for catalytic activity–an “on” switch that you falsely assumed is the norm in life, because you made perfectly rational, obvious predictions (but incorrectly presenting them as facts) from a design hypothesis.

Can you name a single protein complex in life that has the same property?


So let me get this straight: you’re not going to let me explain to you what I meant by the words that I used (which I still think is obvious once I clarify), but are going to insist continuously and forever that what I meant is what you want me to have meant so that you can rant on about how stupid I am. That’s going to make dialog difficult, partly because I’m not going to defend what I didn’t mean.

Let me try one more angle. Let’s look at the opposite of my statement:
“For a protein complex, the location of the binding site on a subunit doesn’t matter in determining if the resulting quaternary structure has meaningful catalytic activity.” That would be clearly wrong. So if the binding site cannot be anywhere, it must be at a “right” location for some catalytic activity to emerge.

Does that help?

The paper is about fluourescence. If you had wanted me to follow particular links, it would have been a whole lot easier if you had just posted those.

But regardless, even following several of those links, you have yet to find a study that shows that the binding site of a complex protein can be anywhere on the subunit, and still provide some catalytic activity.

See? Abusive. And when you go through my post and pick out phrases all over the place to trash on with little one-liners, that’s being nit-picky.

At what point did I even describe you as stupid, much less rant about it?

It would be.

The hypothesis you are sneaking in has nothing whatsoever to to do with where binding occurs. Your (perfectly reasonable) design hypothesis is that quaternary structure turns on catalytic activity.

Can you describe a single case in which that occurs, Marty?

No, the paper is about the usefulness of split GFP.

Which I then did, from the paper, since you don’t seem to want to dig very deeply.

I didn’t claim they did. Your design hypothesis that I am citing has nothing to do with the locations of binding sites. It is far more basic and easily testable.

Your design hypothesis, falsely presented as fact, is that quaternary structure turns on catalytic activity.

Can you describe a single case in which that occurs?

Did I mention that neither the testable design hypothesis you are sneaking in, nor my question, have anything to do with specific binding sites?

How is that abusive?

I often find, to my amazement, that IDcreationists have far less understanding of biology than I would think they do. For example, @Eddie argued with me for months in support of Stephen Meyer’s false claim about peptidyl transferase being a protein without (apparently) even knowing that ribozymes are not proteins.

Given that context, it’s a perfectly reasonable question.

So, back to substance, why is it that humans routinely design split proteins that absolutely require quaternary structure to function, whereas you assumed that this must be the case in vivo while not being able to name a single case?

Why does stripping a myosin hexamer down to half of the heavy chain INCREASE its ATPase activity if your assumption is true?

How many times have I explained that this has nothing to do with the sites of interaction?

This is about an obvious difference between design and evolution. It was so obvious that you assumed that protein complexes in living things have been designed in a particular way.

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There you go again, just repeating your misunderstanding ad nauseum, hoping that will make it true. I think we should rename this forum “Mercer’s remarkable ability to misread simple English.” Your hunt here is beginning to look like the search for WMDs in Iraq.

I hope you’re having fun with yourself!

Looks to me like you’re the one making invalid assumptions – about what I think. If you ever want to know what I actually think, feel free to ask. But you might have to learn to read English for what it actually means, rather than what you want it to mean.

How interesting that you omitted your embedded hypothesis itself: quaternary structure turns on catalytic activity.

That’s how designed, split proteins work. It’s not how natural ones do, as a rule.

No, you told me what you think:

My point isn’t about right or wrong locations of binding sites. I am pointing out something much more fundamental and revealing: your claim about how quaternary structure regulates function:

Can you name a single case in biology in which the catalytic activity requires quaternary structure, as it does for all of these human-designed complexes?

Why do you think that protein complexes in vivo are regulated like intelligently designed (by humans) split proteins?


There’s a more charitable way to read this. Don’t know if it’s the intended point, but it would be necessary for a complement not to be at the wrong location in order for the quaternary structure to retain catalytic activity, i.e. the binding site must not produce a quaternary structure that blocks access to the active site.

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I don’t think that @Marty was proposing anything that complex.

My point can be distilled to a simple question: why can intelligent designers (humans) design modifications of natural proteins to implement quaternary structure as a positive, exquisitely sensitive, binary switch to turn on catalytic activity, while the Intelligent Designer of nature has AFAIK never done so?

We would not expect the iterative processes of evolution to produce them.

Thank you most kindly, @John_Harshman! You nailed it. My first example above stated,

… and here trying to explain by contrast …

I think your summary is an excellent paraphrase of my point.

So, thank you again. I’ll stop there, and hopefully others will, too.

Which doesn’t have anything to do with my point, which is that you were quasi-tacitly assuming that quaternary structure positively regulates catalytic activity.

Why can we design so many split enzymes that do so, while none AFAIK exist in nature?