An Open Letter to Dr. Michael Behe (Part 5)

| 23 Comments

Dear Dr. Behe

It is good to see that you agree that the Golgi targeting sequence is an example of a binding site. However, you don’t get to ignore it because “viral proteins are special”. As I showed in the post you are supposed to be replying to, this is nonsense. In your book you categorically state HIV has developed no new binding sites, the diagram on page 145 of “Edge of Evolution” has a big zero on it. Yet your own example of a binding site is the haemoglobin S mutation, a single amino acid mutation that just clumps up proteins. You don’t write in your book “HIV has evolved several binding sites, but they don’t count because they are viral-protein-host protein interactions” or “HIV has evolved several binding sites, but they don’t count because they are equivalent to the HbS mutation”, you just write zero

Which is wrong.

An again, you are inconsistent, you are perfectly happy to consider viral-protein binding to cellular protein interactions when you think there is no evidence of them evolving (the gp120-cell surface receptor binding, CXCR4 binding anyone). Still, let us accept that you will ignore any viral-protein-cell protein interaction.

Why did you ignore the viroporin section? An example of viral-protein –viral protein interaction that generates a new structure with important functional consequences. This is a direct challenge to the very heart of your argument.

But let’s return to the Glogi binding site sequence, YRKL. Yes, the precursor of that sequence can be seen in SIVcpz/gab, the ancestor of HIV-1 M. Very likely it did come about by a sequence of intermediate selectable steps, indeed this is the most likely way all binding sites come about, rather than your unrealistic, unevidenced model of multiple amino acid changes needing to occur simultaneously.

To see why, lets look at a general model of protein-protein binding; peptide binding to an important hormone receptor, the angiotensin II (AT) receptor (there are two version of this receptor, but for simplicity I will consider only one, the AT1-R).

Before going on, I’ll talk briefly about conceptualizing binding. Binding of a protein to another entity, whether another protein, a peptide of a small non-protein molecule, can be likened to a lock and key arrangement. Surface structures on one entity (the “key”, be it protein, peptide or small molecular), fit into complementary structures on to the protein (the “lock”). This model of course is too simple, firstly electrostatic charge and the “oiliness” [1] of the binding entities play as important a role as shape. Secondly, both the lock and the key are “floppy”, unlike our familiar locks and keys proteins, peptides and small molecules can flex and stretch into different shapes. This way a diverse number of molecules can bind to the same binding site (otherwise we wouldn’t have drugs, which mimic often bizarrely, natural hormones and enzyme substrates). With the image of a “floppy” lock and key in our minds, let’s proceed.

lock&key.gif

Binding of ligands to proteins like enzymes or hormone receptors has been likened to a “lock and key” arrangement, where the molecule fits into a space in the protein in a similar manner to a key fitting into a lock. While a useful analogy to help us visualise things, this image can be misleading as we will see, as various binding interactions are important, not just physical “lumps and bumps”. Here I have used a molecule of adrenaline to illustrate the concept.

The AT1 receptor is a 359 amino acid long protein which binds the peptide angiotensin II (AII) and related peptides. AII and similar ligands bind to a specific amino-acid sequence in the AT1 receptor, DNKH in the one letter amino acid code.

D(Aspartate 281) N(Asparagine 111) K(Lysine 199) H(Histidine 256)

These amino acids are not contiguous, but separated across different loops of the protein, forming a lining to a pocket in the protein molecule.

at1a.gif

The three dimensional cartoon structure of the AT1-receptor with AII bound. We are looking at the receptor from above, with some chains removed for clarity. The transmembrane helicies are shown as grey coils, AII is shown in yellow, the DNKH amino acids are shown in red. See http://home.mira.net/~reynella/chime/ang_tuta.htm for 3D structures (needs MDL CHIME plug-in to view and manipulate the 3D structure).

As I said above, the AT receptors bind angiotensin and similar peptides to the ligand binding site. As with the receptor, not all of the ligand sequence binds to the binding site. While here we are talking about small molecules, the principle is the same for segments of larger proteins binding to another protein. The sequences of ligands are shown in the one letter amino acid code, with the amino acids that bind being shown in bold.

AII DRVYIHPF
AIII RVYIHPF
SarIle SRVYIHPI
SarAsp SDVYIHPI
CGP NYKRHPI
AIV VYIHPF

Now, if you only looked at AII and the related hormone AIII, you would believe that three binding sites RYF, were required for binding. You might puzzle over how you could simultaneously get three replacements in an ancestral, non-binding peptide so that it would bind to this site.

But as we look at SarIle and SarAsp, we can see a way. These have only two of the three binding amino acids present in AII and AIII, yet they bind very well indeed. Maybe only binding to the the DN part of the DNKH motif in the AT-1R is critical. However, AIV, which dones not have a D binding amino acid, still binds (not as well as the others, but it still binds enough to be selected), so we can see selectable binding can come about more simply, and via different pathways.

It can be even simpler than that. The hormone CGP binds to completely different amino acid’s in the ligand binding cleft, not DNKH at all, so there more than one way to get to bind specifically to a something as highly selective as a hormone receptor binding site. In terms of the lock and key mechanism, your claim, Dr. Behe, is that all tines of the “key” must be in place simultaneously to fit in the lock. But as we have seen above, this is not correct, even a very simple “key” will fit into the lock (keeping in mind both the lock and key are “floppy”).

All we need to get Darwinian selection of binding sites is to have weak but selectable binding. This can be accomplished with very simple changes, and a variety of unrelated structures, even for very highly restricted structures. Note again, while this example is small peptides binding to a receptor, a small peptide is in principle the same as a surface loop of a protein binging to another protein. Your model of highly restricted sequences which have to be in position simultaneously is just wrong.

So now Dr. Behe, keep this in mind, and reflect on Wang (2002) again, and paying particular attention to the role of amino acid F43 in binding of proteins such as gp120 to CD4.

Yours sincerely
A male featherless biped named Ian Musgrave
[1] Some amino acids are charged, and will bind to other charged amino acids, some are “oily” and will bind to other oily amino acids.

23 Comments

Shorter Michael Behe: “Amongst my weaponry is vagueness, reptition, ruthless goalposts shifting and an almost fanatical refusal to acknowledge that I’ve been reamed.”

Or even better: The Edge of Evolution is just outdoor behind all known and documented mutations. Not that any of those are interesting so let’s rename my book as The Edge of interesting evolution.

So basicly, edge of interesting evolution is past by known mutations, it is in the unknown mutations where lies my intelligently interesting design.

If only we could have gotten scientists to critique Darwin as much.…

If only we could have gotten scientists to critique Darwin as much

Feel free to do so, Bach. Show your work though.

Bach Wrote:

If only we could have gotten scientists to critique Darwin as much…

I guess you never heard of Gould, Kimura, Kauffman - or “blended inheritance.”

BTW, do you agree with Behe on common descent or not?

Frank J you forgot Lord Kelvin as well

Bach:

If only we could have gotten scientists to critique Darwin as much.…

What do you think they’ve been doing the for the past 150 years? That’s why evolution is so well founded and robust. Evolutionary theory has been extended, clarified and refined in the face of relentless “criticism” in the form of scientific scrutiny for so long that it has rightly earned it’s place as the bedrock of all biology.

“Intelligent Design” on the other hand, was the stillborn offspring of “creation science” which had folded almost instantly in the face of the most superficial scientific scrutiny.

The Discovery Institute just tied the corpse of creation science up with marionette strings and called it Intelligent Design. But you only get one weekend at “Bernie’s” before the corpse starts to smell too much to fool anyone anymore.

Bach:

If only we could have gotten scientists to critique Darwin as much.…

What do you think they’ve been doing the for the past 150 years? That’s why evolution is so well founded and robust. Evolutionary theory has been extended, clarified and refined in the face of relentless “criticism” in the form of scientific scrutiny for so long that it has rightly earned it’s place as the bedrock of all biology.

“Intelligent Design” on the other hand, was the stillborn offspring of “creation science” which had folded almost instantly in the face of the most superficial scientific scrutiny.

The Discovery Institute just tied the corpse of creation science up with marionette strings and called it Intelligent Design. But you only get one weekend at “Bernie’s” before the corpse starts to smell too much to fool anyone anymore.

Frank J:

Bach Wrote:

If only we could have gotten scientists to critique Darwin as much…

I guess you never heard of Gould, Kimura, Kauffman - or “blended inheritance.”

BTW, do you agree with Behe on common descent or not?

Don’t blame Bach, he doesn’t know how to read books.

Behe is still opening up with misdirections (“high dudgeon”, “epidemiological factors”) and avoiding the issue.

But now he is starting to show the pressure of defending his indefensible claims without admitting his errors. He has to jump from “it may affect epidemiological properties unpredictably” to “a very restricted envelope of biochemical possibilities”. Of course, he would like to pretend that the restriction to the discussed mechanism of LTR variations means some known restriction of possible traits, against the very quotation he uses, but it is a visible failure.

And to pitch in with Tyler, isn’t it funny how Dr Behe claims that HIV now suddenly can go through complex mutations, yet somehow fails to evolve for Behe, yet evolves visibly for scientists? It seems Behe has his edge where his conceptual myopia is.

I guess you never heard of Gould, Kimura, Kauffman - or “blended inheritance.”

And then we have to remember that Darwin constructively proposed a theory and its mechanisms, while Behe runs errands for a religious movement by proposing unsupported obstructions. Darwin certainly got his share of religious criticism from bishop Wilberforce using Payley’s watchmaker argument, the same argument that Behe is using. (“Parts working together must have been poofed together by design, not evolved naturally by verified biological mechanisms.”)

That would make Phillip Johnson the pope of the ID church of poofters…, um, Payleism.

Call it a pathological “meme” or the “imp of the perverse”: Behe is clearly the thrall of some tightly embedded idea that won’t let him go. Pity him, because it is methodically undoing the decades of effort he spent building up his credibility in the scientific community.

I guess Bach never watched Judgment Day. I loved the part where Miller pointed out that evolutionary theory makes specific predictions about what modern genetics should discover. Darwin had no idea of any of this and yet, as Miller pointed out, modern genetics confirms evolutionary theory in great detail. The example of the fusion of human chromosomes was a classic.

All Bach has left is denying all of the evidence just like Behe. Just pretend Darwin is some kind of saint to be idolized rather than a real scientist whose ideas are tested every day. That sure makes it easier to ignore all of the discoveries of science in the last 150 years. What does he think people are doing when they study the genetics of Galapagos Finches or peppered moths in England? The entire field of evo-devo is basically one big test of Darwin’s idea. Any of these studies and thousands more could have proven Darwin wrong, they just didn’t. Darwin is the most scrutinized person in all of history, personally and professionally. But he was right. Deal with it, grow up, get a life, do some real research and stop spouting nonsense already.

I think ID movement is very very damaging to the religious establishments. These IDiots might not care who gets damaged but all their lying, perjuring, running stealth candidates to school boards, trying to sneak God into schools with a wink-and-a-nod etc are creating an impression that all religious people are close minded, anti-science backward folk. And it is really damaging the religious institutions.

I think we should talk past these IDiots and to the religious leadership. We need to show them how damaging ID movement is to their religion. May be they will be able to rein in these dolts. Or at least they will cut off the money supply and those who are leeching off ID movement for personal financial gain would go away.

These IDiots are simple organisms that have established themselves in an ecological niche, attack-science-get-support-from-the-pious. They will mutate and survive as long as there are nutrients (money) in that niche. How long can we be squirting Round-Up on these dolts? Let us also spread a little crab-grass preventer germination inhibitor in the pious crowd.

Just curious to know if Behe responded to any of these “open letters”?

Why did you ignore the viroporin section? An example of viral-protein –viral protein interaction that generates a new structure with important functional consequences. This is a direct challenge to the very heart of your argument.

I think you answered your own question there.

LOL @ Mr. Chris

Well, Behe is ‘responding’ to Ians first open letter, but only because his publisher was inundated with emails from people outraged at his initial sexist ‘response’ to my essay.

Notice how Behe is really addressing my comments, but under the pretenses of responding to Ians letter. Behe still cant lower himself to respond to some woman.

LOL! What a wretched creature!

I just wanted to confirm Behe is ignoring all these “open letters” Sounds like he is.

What a dufus. These “open letters” are the closest thing Behe/ID will ever get to peer review and I can’t help but note he’s ignoring the review and his own scientific peers. Classic example of intelligent design in action.

And they whine about peer review.

I’d suggest a a final summary “open letter” to Behe that documents each issue that was brought forth and also Behe’s response or lack thereof. I really think you guys are on to something with these “open letters”. It demonstrates our willingness to engage the ID community in scientific inquiry.

I hope PT will keep these “open letters” going. I think presenting informal “peer review” like this for other IDists who portray themselves as scientists would be a good idea. I like the “open letter” approach where the writer is encouraged to respond to specific criticisms versus simple critiques of what they have written.

Let’s hope we see some “open letters” to Dembski and Wells soon.

Chris

David Stanton Wrote:

Any of these studies and thousands more could have proven Darwin wrong, they just didn’t.

Ironically, because evolution is so well supported and fulfills so many predictions, hardly anyone anymore considers it even worth mentioning what the “next best candidate” could have been. Unfortunately that helps the IDers with their evasion scheme. Before the “big tent” strategy was firmed up, Behe conceded mainstream science’s conclusion on the age and common ancestry of life, and no one in ID challenged him directly. So it seems that they know that the best they could have hoped for is a Goldschmidt “hopeful monster,” or perhaps Behe’s own “designed ancestral cell.” But neither would be any comfort to YECs or classic OECs. Furthermore, the fact that they haven’t even tried to take on Douglas Theobald’s 29+ potential falsifiers strongly suggests that they have long known that even the “next best candidates” would be doomed to failure.

When “next best candidate” is mentioned, I immediately think of Gert Korthof’s web site which covers the alternatives:

http://home.wxs.nl/~gkorthof/

What a dufus. These “open letters” are the closest thing Behe/ID will ever get to peer review and I can’t help but note he’s ignoring the review and his own scientific peers. Classic example of intelligent design in action.

The peer-review process can be brutal, but it serves a purpose. Behe will have been through this in his former career as a scientist so he can brush off criticism without taking any notice. Besides, he hasn’t written these books with a scientific audience in mind (when was the last time he did any science?), so to correct any ‘mistakes’ he may have made would make him look foolish. Ask any of his followers - he is infallible. Peer review is beyond this pseudoscientist.

Tom,

Korthof’s site, perhaps more than any other resource, shows that “equal time” for any POV about evolution, scientific or not - is yours for the asking (so much for the outrageous charge of censorship). And yet, as I wrote on the other thread about Frank Sonleitner’s critical analysis of “Panda’s,” the DI ironically has no interest in promoting it. Because of course they have no interest in either “equal time” or a true critical analysis. In fact, for those IDers who seem to deny common descent, even if they find it politically incorrect to challenge Behe directly, they could always tout Schwabe or Senapathy, and find their references easily at Korthof’s site. But there too, there’s almost dead silence.

The ID community complains the’ve been shut out from mainstream science. Yet here Dr Musgrave has posted 5 open letters to Dr Behe in attempt to engage him in a discussion regarding assertions Behe claims are scientifically valid.

These “Open Letters” are the closest Behe/ID has come to “peer review” and still Behe ignores every single attempt to engage him in a science based discussion.

What the hell does that tell us about Behe, or ID for that matter?

Knowing that Behe doesn’t submit ANY of his ID writings for peer review says volumes about ID and Behe’s confidance that his ideas will stand up to that sort of scrutiny. Ignoring these Open Letters tells us even more about Behe and his ideas.

It makes sense that Demsbki doesn’t submit his work to peer-review or that he ignores PT. Dembski is a two bit bible teacher who probably can’t make sense out of his own math. It makes sense that Wells does not submit his work to peer-review, he’s a clown with a PhD who’s admitted spiritual ambition is to “defeat darwinism” for God. Clearly neither Dembski nor Wells are scientists. But Behe, on the other hand, teaches college level science for God’s sake and therefore has a responsibility to his students and his scientific peers to answer for his own work and ideas. Not to mention he has a responsibility to his employer.

This is simply pathetic.

Mr_Christopher Wrote:

What the hell does that tell us about Behe, or ID for that matter?

The DI just hired long time Bigfoot advocate Michael Medved as a senior fellow. So I guess we will soon hear whether Behe thinks that humans share common ancestors with Bigfoot (probably yes), and whether evolution caused Bigfoot to diverge from the last common ancestor (probably not). Either way, he’ll probably still keep us guessing when and where any design actuation events occurred.

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This page contains a single entry by Ian Musgrave published on November 15, 2007 12:04 AM.

Post-Nova stuff was the previous entry in this blog.

Evolution: The Fossils Say Yes! is the next entry in this blog.

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