Proteins have very different functions depending on the family. The weakness that I see from your side is conflating that data from one protein family can be extrapolated to all proteins. The functional hills are an example. It works ok for enzymes but how about a protein that is a piece of a much more complex process.
You have always made an effort to support your claims. Both sides are facing the same issue and that is what we know about these complex cells is very limited at this point.
The factory in china is in flames.
Yeah. Proteins with different functions from different families, have different functions. Who knew?
But you donât see that anywhere. Youâre making it up. Nobody actually does this.
The functional hills are an example.
Of what? âThe functional hillsâ is an example of what? Of âconflating that data from one protein family can be extrapolated to all proteinsâ? No, itâs not an example of that. Itâs not even clear what the heck youâre even talking about with âthe functional hillsâ.
Youâre blathering again Bill. Just spewing out barely coherent sentences and ideas.
The sample size just defines the confidence level. You have something more here which is certain positions favor certain amino acid types. There is a real clue here which allows you to characterize substitutability. This work is just starting but it has promise. @Art critique of Axe goes through the different methods of this type of estimate. @Art is coming to a different conclusion then the ID guys and that is fine at this stage.
Over all it depends on what you need to know. It depends how much accuracy we need for our conclusion.
You may just want a relative measurement. We know there is a difference in constraint which has 99% sequence equivalence and one that has 10% equivalence given the same time separation.
What is the confidence level then? Plus or minus two hundred orders of magnitude?
This is exactly what you do when you claim Axe is 65 orders of magnitude off in his estimates. Until you repeat his experiment in the same conditions you donât know. @Art agreed that Axeâs number was similar to other experiments of the same type.
This is exactly what @Mercer is doing when he claims measured catalytic activity in e coli bacteria is the same as the catalytic activity required for e coli to survive in a penicillin contaminated environment.
If that is the error band at this point so be it with gpuccios method. Prp8 has been estimated (gpuccioâs method) at 4000 bits of FI. 3400 to 4600 works given the magnitude of the number. Again simply having a relative measurement is ok at this point.
No. When I say Axeâs number is off by 65 orders of magnitude, I am rebutting the implicit (some times explicit) claim being advanced by places like EN&V*, and in books like Darwinâs Doubt, that Axeâs number can be generalized to all of sequence space. In other words, I am showing their generalization to be wrong. I am not claiming all functions are found at a frequency 65 functions below that advanced by Axe. I am rebutting their claims by finding examples of functions that are that much more frequent.
Repeating what I wrote back then:
Notice the last part I highlighted in bold. This is apparently what most ID-creationists believe, because this is what the higher-ups in the ID movement claim that Axeâs research shows. (âŚ) This is also what your average ID proponent today believes. This is the number they read in books like Darwinâs Doubt, is pushed on EN&W and they believe this number corresponds to the odds of finding anything functional in 150 amino acid-sized sequence space . I donât see how you can believe this isnât what Axe, Meyer and colleagues wants them to believe, because theyâve never taken even a single step to correct that misapprehension.
I also go on to explain that Axeâs claim simply canât be generalized to all functions. I state:
For those reasons, Axeâs number just canât be trusted as an estimation of that. It is a number that represents an estimate of a single very particular thing, which is the frequency of sequences 150 amino acids in length, that adopt the known Beta-lactamase fold and catalyze break down of ampicillin. For that reason it is NOT an estimate of the frequency of all functional proteins in all of 150 amino acid sequence space.
Youâve completely forgotten everything I wrote back then it seems.
Bill is just blowing up those irony meters faster than the factory can churn them out.
Very good explanation thanks. You are saying you cannot generalize as Art is saying and I agree with you. Axeâs paper is a data point and the data showed a 10^-77 chance of the specific e coli strain surviving in a measured concentration of penicillin.
It is not 65 orders of magnitude off. The experimental results not representing all applications is more appropriate.
Your point here is valid.
Axeâs EXTRAPOLATION, from a single experiment in which he couldnât be bothered to measure enzymatic activity, is 65 orders of magnitude different from literally thousands of studies that have measured functional space in the correct, forward direction.
His experiment was deliberately designed not to measure the capabilities of evolution, but were designed to provide a data point for political purposes.
I have never claimed anything like that. Would you please provide a direct quote from me or retract your claim?
Iâm fairly confident that there is no single fold.
If you say you never made this claim I will accept that. Apologies for misrepresenting you.
Correct. But you omitted that he started with a temperature-sensitive mutant, not the wild-type protein. Why?
Axeâs extrapolation of that experiment to all of sequence space is.
Youâre conflating this tiny experiment, that could have been done by a graduate student in a week, with Axeâs unwarranted extrapolation of it, Bill.
Do you have evidence of this. @Art claimed it was others who made this extrapolation.
So am I. My understanding is that there is a huge ensemble of possible 3dimensional conformations a protein can take, and you can always pick out some small subset of such similar conformations and call them a âfoldâ. But changes the sequence enough in the correct spots, that âfoldâ will start to change, and youâll get overlap to other such, more or less arbitrarily defined clusters of similar structures.
And Axe ignores them, such as catalytic antibodies.
The ID guys are ignoring most of the relevant evidence.
Thatâs some pretty amazing projection youâve got going there, Bill.
How many proteins did Axe analyze before he called it done, 15 years ago?
If Axe thought that his extrapolation was valid, he would have repeated it again with many other proteins.
You need to make sure you are not misrepresenting Axe.