Is Helicase a House of Cards?

[T_aquaticus]

@stcordova

If you encountered a table that had 500 fair coins 100% heads would think the 100% condition was the result of design or chance?

I don’t see how that applies to evolution.

A bit of added explanation . . . I went to a webtool that produces random protein sequences and got this result for a 100 residue protein:

QAVTYAGGGMMKATETFEELDASVTLPLCIKLGPHGTVNAHSEMGRWVVFEWQHNIISQPRTDIEAKWSGCPIWPQMFFHEMIYEPALTVDLNIEWWHPG

The chances of any specific 100 aa protein is 1x20^100. Therefore, the chances of getting that protein was 1 in 1.6x10^260. According to ID arguments, there is no way that a random sequence generator could have produced that rare of a sequence, yet it did. In fact, I can keep doing this with ease.

[swamidass (S. Joshua Swamidass)]

@T_aquaticus

According to ID arguments, there is no way that a random sequence generator could have produced that rare of a sequence, yet it did. In fact, I can keep doing this with ease.

According to ID arguments, the random generator was designed

[stcordova (Salvador Cordova)]

@T_aquaticus

I don’t see how that applies to evolution.

Maybe it doesn’t.

I have not worked out the details yet, but I think proteins with Quaternary structure (lock and key type interactions), something like violations of normative expectation could be worked out.

Alternatively, something could be estimated for the violation of expectation of metal-binding proteins since the fold is easier to resolve. The simplest example of metal-binding proteins are Zinc Fingers which, when functional, must have a lock-and-key type interaction with DNA. CTCF is a zinc finger protein that binds to about 55,000 locations on chromatin to create regulatory loops. Haemoglobin has been on my mind too.

I don’t think there is a way to apply the law of large numbers to such situations as protein sequences elegantly, but one can still frame the issue in terms of a violation of some sort of physical/chemical expectation.

EDIT: 13:09 EST for clarity

[T_aquaticus]

@stcordova

I have not worked out the details yet, but I think proteins with Quaternary structure (lock and key type interactions), something like violations of normative expectation could be worked out.

Antibodies are a perfect model for this process. VDJ recombination produces random sequences in the binding domains of antibodies, and this process regularly produces lock-key binding among millions to billions of clones.

@stcordova

I don’t think there is a way to apply the law of large numbers to such situations as protein sequences elegantly, but one can still frame the issue in terms of a violation of some sort of physical/chemical expectation.

From my reading of the literature, functional sequence is much more common in sequence space than some think.

[stcordova (Salvador Cordova)]

@T_aquaticus

From my reading of the literature, functional sequence is much more common in sequence space than some think.

Agreed, if one has a low bar of function, like some random catalytic or inhibitory capability.

However, the bar is higher for proteins with symmetric quaternary structures like the helicase below where 6 proteins/polypeptides assemble symmetrically. This is the Helicase Homohexamer enzyme. It doesn’t have the requisite catalytic/enzymatic activity unless it adopt something like this geometry so it can build this ring-like structure. Each of the colored segments is a copy of the helicase protein.

[T_aquaticus]

@stcordova

However, the bar is higher for proteins with symmetric quaternary structures like the helicase below where 6 proteins/polypeptides assemble symmetrically.

How so?

[stcordova (Salvador Cordova)]

As an aside, it is inelegant to use violations of the law of large numbers to say the following structure is designed, but it is clearly a violation of normative expectation since random starting coordinates and orientations of the cards will not achieve this macrostate. The most common macrostate of random coordinates and orientation for cards is for them to lie flat on the table, it is exceptionally rare they can be made to stand up like this.

This is analogous to the problem of certain quaternary structures in proteins.

[stcordova (Salvador Cordova)]

How so?

Good question, I’m working with some biochemists and hopefully some day a structural biologist and/or biophysicist to demonstrate why this is so.

[stcordova (Salvador Cordova)]

Sure, this is an important enough topic.

[Faizal_Ali]

@stcordova

As an aside, it is inelegant to use violations of the law of large numbers to say the following structure is designed, but it is clearly a violation of normative expectation since random starting coordinates and orientations of the cards will not achieve this macrostate.

The “Law of Large Numbers” seems to keep coming up in these discussions. I had never heard of the term, so I looked it up. I know Wikipedia is not always the most reliable source, but if this article is correct the law seems to have very little to do with what we are discussing, and has little relevance to ID Creationism:

Law of large numbers

[stcordova (Salvador Cordova)]

and has little relevance to ID Creationism:

I’m aiming to change that!

[stcordova (Salvador Cordova)]

This is a wiki article on quaternary structure, it represents my views on the definition.

Protein quaternary structure

Many proteins are actually assemblies of multiple polypeptide [protein] chains. The quaternary structure refers to the number and arrangement of the protein subunits.

Unfortunately the word “protein” and polypeptide are not clearly delineated in the literature and are used interchangeably. But with respect to a TYPICAL helicase there are

6 identical copies of the helicases protein/polypeptide that are coded from a single helicase gene. The 6 copies must them be assembled by a machine called a ring loader that puts the 6 copies into the complex in the diagram (there are some variants of six copies, like 12 copies, etc.).

Then when helicase is done doing it’s job, there is a ring breaking machine.

Some enzymes like topoisomerase will spontaneously form quaternary structures in vitro in solution to look like this complex made of two topoisomerase polypeptides/proteins:

There are some functional enzymes with quaternary structures that I think violate expectation from random amino acid sequence. I’m presently exploring how difficult it is for random sequences to create functional quaternary structures. This is problem in bio-physics.

In a pre-biotic scenario, like Sidney Fox’s proteinoids, for sure, homo-meric quaternary structures of any length above 100 is astronomically remote as a matter of principle, unless we have a trivial senario of only one species of amino acid in the soup! This is because we don’t expect random sequences to be duplicated.

Just that duplication alone in a pre-biotic context, would be a violation of the law of large numbers, if the assembly were random.

Homo Sapien helicase polypeptide is 1270 residues long, forming a complex (like that shown above) would require 7620 residues.

If even 100 or so residues are critical to making the fold and the connection interfaces such that they can fit snugly around DNA this would be an astronomically remote event, perhaps comparable to a house of cards forming spontaneously by gust of wind.

For the reader’s benefit, here is a 2-minute animation of Helicase in action:

- YouTube

[Giltil (Gilbert Thill)]

@T_aquaticus

According to ID arguments, there is no way that a random sequence generator could have produced that rare of a sequence

This is utterly false. Clearly, you don’t understand ID theory.
Ok, Using a random sequence generator, you came across the following sequence:
QAVTYAGGGMMKATETFEELDASVTLPLCIKLGPHGTVNAHSEMGRWVVFEWQHNIISQPRTDIEAKWSGCPIWPQMFFHEMIYEPALTVDLNIEWWHPG
According to ID theory, because this sequence doesn’t match any SPECIFICATION, no design inference is warranted.
But what if using another random sequence generator, you would have come across a sequence that perfectly matched the first 100aa of the human myoglobin gene? In that case, according to ID theory, you would be warranted to conclude that the random generator was not a random generator after all. IOW, you would be entitled to draw a design inference. Why? Because in that case, the sequence would match a SPECIFICATION.
As you can see, specification is the pattern that signifies intelligence.
https://pdfs.semanticscholar.org/ffc2/8808451d271cd1d520e1a95beed72ee41aaa.pdf?_ga=2.29015995.603540201.1566413746-737648290.1521213557

[stcordova (Salvador Cordova)]

Like a key being able to operate a lock, or a part of a machine that must fit snuggly into another part, so is the case with functioning Quaternary structures being made possible.

http://dl.clackamas.edu/ch106-08/quaterna.htm

the bonds involved in holding these separate chains together can be van der Waals bonds, hydrogen bonds, ionic bonds, or at times covalent bonds.

The problem of helicase is comparable to building a motor with the parts properly fit. There may be an infinite number of ways to build a motor, but the structure of one part limits the way the other parts can be made such that the overall whole is functional. Randomly concocted parts won’t work! It is the geometry and fitting requirement that make helicase improbable as a life-critical protein.

I might have chosen the flagella as an example, but I prefer helicase since it is a life-critical enzyme and because it’s quaternary structure is easy to see just by looking at it.

For helicase, the copies must connect to each other nicely, and then be just the right size so that can wrap around DNA, and one other thing, it needs a place where ATP can dock to power the this “motor” like device. Then there are the connecting locations, somewhat like the way things are made to snap together. The complex seems to require foresight and planning, because life needs more than quaternary structure that just makes a pretty hexagon-like structure, the hexagonal structure has interact with Atp and DNA like a machine that is methodically unzipping the DNA as in the above video.

The law of large numbers precludes a Urey-Miller soup followed by random polymeraization as an explanation for the formation of helicase-like proteins where there are identical copies of polypeptides about 1000 amino-acids long. The odds of this happening is like shuffling decks of cards randomly and getting the same sequence 6 times in a row. The odds are astronomical.

One might of course invoke and RNA/DNA world, but this has it’s own problems. If we have a DNA-based genome, it’s unlikely the creature would survive without helicase, and helicase won’t exist without a gene storage mechanism like DNA that contains the blueprint for the helicase polypeptide.

[Mercer (John Mercer)]

@stcordova

Agreed, if one has a low bar of function, like some random catalytic or inhibitory capability.

False. We’re talking about specific catalytic capabilities for catalytic antibodies.

@stcordova

However, the bar is higher for proteins with symmetric quaternary structures like the helicase below where 6 proteins/polypeptides assemble symmetrically.

Binding is no big deal. The Kd of antibodies for antigens is typically in the nanomolar range.

@stcordova

It doesn’t have the requisite catalytic/enzymatic activity unless it adopt something like this geometry so it can build this ring-like structure.

Interesting. Precisely how did you make this determination of fact? Which assays did you do?

I suggest that you try some protein purification before pontificating on the unlikeliness of multimerization.

@Giltil

This is utterly false. Clearly, you don’t understand ID theory.

There’s no such thing. How can one understand or not understand something that doesn’t exist?

[Roy (34-year veteran)]

@Giltil

@T_aquaticus

According to ID arguments, there is no way that a random sequence generator could have produced that rare of a sequence

This is utterly false. Clearly, you don’t understand ID theory.

he clearly does understand ID theory, and you’ve just as clearly been suckered by it.

Ok, Using a random sequence generator, you came across the following sequence:
QAVTYAGGGMMKATETFEELDASVTLPLCIKLGPHGTVNAHSEMGRWVVFEWQHNIISQPRTDIEAKWSGCPIWPQMFFHEMIYEPALTVDLNIEWWHPG
According to ID theory, because this sequence doesn’t match any SPECIFICATION, no design inference is warranted.

Where is the SPECIFICATION for the helicase protein?
By your own argument, if you can’t produce one, no design inference is warranted.

Cue back-pedalling and special pleading…

[stcordova (Salvador Cordova)]

@Mercer

Interesting. Precisely how did you make this determination of fact? Which assays did you do?

Basic molecular biology, unless you want to argue before everyone here that random sequences can do the job of helicases. We do know, for example disruption of helicase activity is bad.

New Insights Into DNA Helicases as Druggable Targets for Cancer Therapy

Molecular defects in the RecQ helicases give rise to genomic instability, and mutations in WRN, BLM, and RECQL4 are linked to hereditary diseases characterized by accelerated aging or associated with cancer

But you said:

I suggest that you try some protein purification before pontificating on the unlikeliness of multimerization.

I was speaking of multimerization in a functional in vivo context, not some lab purification.

[stcordova (Salvador Cordova)]

This again is an animation of the structure and function of one class of helicase:

YouTube

Dr. Mercer is invited to explain the evidence that suggests random sequences can create something that functions like the helicase in the animation. Without it, the cell lineage is effectively dead – so its obviously a problem that must be solve for abiogenesis and/or early evolution.

[Faizal_Ali]

@stcordova

For helicase, the copies must connect to each other nicely, and then be just the right size so that can wrap around DNA, and one other thing, it needs a place where ATP can dock to power the this “motor” like device. Then there are the connecting locations, somewhat like the way things are made to snap together. The complex seems to require foresight and planning, because life needs more than quaternary structure that just makes a pretty hexagon-like structure, the hexagonal structure has interact with Atp and DNA like a machine that is methodically unzipping the DNA as in the above video.

The law of large numbers precludes a Urey-Miller soup followed by random polymeraization as an explanation for the formation of helicase-like proteins where there are identical copies of polypeptides about 1000 amino-acids long. The odds of this happening is like shuffling decks of cards randomly and getting the same sequence 6 times in a row. The odds are astronomical.

One might of course invoke and RNA/DNA world, but this has it’s own problems. If we have a DNA-based genome, it’s unlikely the creature would survive without helicase, and helicase won’t exist without a gene storage mechanism like DNA that contains the blueprint for the helicase polypeptide.

You are assuming that helicase must have arisen in its present form, performing the exact function it now does in the exact same way, from the outset with no precursors.

That is not how evolution works.