# The Argument Clinic

**URL:** <https://discourse.peacefulscience.org/t/the-argument-clinic/15561>\
**Category:** Side Conversation\
**Tags:** Comments\
**Created:** [November 22, 2022, 2:16pm UTC](https://discourse.peacefulscience.org/t/the-argument-clinic/15561 "2022-11-22T14:16:20Z")\
**Posts on this page:** 1\
**Showing post:** 2582

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**Author:** ![Mercer](https://avatars.discourse-cdn.com/v4/letter/m/e274bd/32.png) [@Mercer](https://discourse.peacefulscience.org/u/Mercer)\
**Post date:** [June 3, 2024, 11:49am UTC](https://discourse.peacefulscience.org/t/the-argument-clinic/15561/2582 "2024-06-03T11:49:03Z")

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[Mercer](https://discourse.peacefulscience.org/u/mercer)

> [@The DI responds to my now--two-years-old review of ROTGH](https://discourse.peacefulscience.org/t/the-di-responds-to-my-now-two-years-old-review-of-rotgh/16709/36):
>
> > [@Detwiler: Questions Behe, Polyphen, and Ratchets](https://discourse.peacefulscience.org/t/detwiler-questions-behe-polyphen-and-ratchets/5088/97):
> >
> > > [@Detwiler: Questions Behe, Polyphen, and Ratchets](https://discourse.peacefulscience.org/t/detwiler-questions-behe-polyphen-and-ratchets/5088/97):
> > >
> > > > [@Detwiler: Questions Behe, Polyphen, and Ratchets](https://discourse.peacefulscience.org/t/detwiler-questions-behe-polyphen-and-ratchets/5088/63):
> > > >
> > > > Which is interesting and curious in it’s own right I agree, but that hardly constitutes a trend I feel comfortable extrapolating to a general phenomenon for most proteins.
> > > 
> > > I don’t think it’s that curious. I think that my saying that the direction of a process is _ **basically 50/50** _ is saying that there’s NOT a trend.
> > 
> > LOL. Was that not clear, Mikkel?
> 
> Your responses are getting pitiful, seriously.

You can’t be serious.

> [@The DI responds to my now--two-years-old review of ROTGH](https://discourse.peacefulscience.org/t/the-di-responds-to-my-now-two-years-old-review-of-rotgh/16709/36):
>
> Saying it’s 50/50 is to say what the trend is: In your opinion the trend is 50/50.

You appear to have a strong tendency to misrepresent qualified statements as not qualified. What drives this?

“ **Basically** 50/50” in opposite directions is not a trend. 70/30 in opposite directions is not a trend, either.

Why did you omit “basically”?

> [@Detwiler: Questions Behe, Polyphen, and Ratchets](https://discourse.peacefulscience.org/t/detwiler-questions-behe-polyphen-and-ratchets/5088/44):
>
> > [@Detwiler: Questions Behe, Polyphen, and Ratchets](https://discourse.peacefulscience.org/t/detwiler-questions-behe-polyphen-and-ratchets/5088/35):
> >
> > But apparently mutations towards higher stability are less likely on average compared to mutations towards lower stability. It is true that stability increasing mutations are not necessarily function improving.
> 
> It’s also true that mutations that increase stability of a purified protein in solution can easily decrease the stability of the complex in which most that protein functions.
> 
> So absent encyclopedic knowledge, 50/50 is the best estimate.

5 years later, we don’t have encyclopedic knowledge.

> [@Detwiler: Questions Behe, Polyphen, and Ratchets](https://discourse.peacefulscience.org/t/detwiler-questions-behe-polyphen-and-ratchets/5088/57):
>
> What you are saying with stability is different. It has better definition, but still suffers, as @Mercer has explained.
> 
> As for @Rumraket clarifies he means there is about. 65%-70% chance that a muation will reduce stability in a folded protein. I don’t object to this. _ **That is essentially 50/50** _, and it is self limiting too.

> [@The DI responds to my now--two-years-old review of ROTGH](https://discourse.peacefulscience.org/t/the-di-responds-to-my-now-two-years-old-review-of-rotgh/16709/36):
>
> But it _isn’t_ 50/50 (the average mutation is actually destabilizing on protein structure as empirical studies **designed to get at the tendency** shows)

Really? What kind of proteins? All? Average ones, or only a particular type? It’s _ **literally** _ there in the first word of the Introduction.

What do we know about the biophysical process by which that particular type of protein folds?

> [@The DI responds to my now--two-years-old review of ROTGH](https://discourse.peacefulscience.org/t/the-di-responds-to-my-now-two-years-old-review-of-rotgh/16709/36):
>
> …your supervision of your postdocs and students finding 8 stabilizing mutations in alpha-tropomyosin doesn’t show that it’s 50/50.

Again, you employ a blatant straw man fallacy. My pointing out that 8 for 8 is unremarkable is not a claim that it demonstrates “50/50.” How could it? What did I write in the discussion of that paper? Did you forget that they also had opposite effects on contractility?

> [@The DI responds to my now--two-years-old review of ROTGH](https://discourse.peacefulscience.org/t/the-di-responds-to-my-now-two-years-old-review-of-rotgh/16709/36):
>
> You finding cases where mutations (to active sites, for example) are stabilizing is a textbook example of cherrypicking.

Your pretending that a study explicitly limited to a specific structural subset of proteins is universal isn’t cherrypicking?

IMO, the best we’ve got to reflect what’s going on _in vivo_ are the collections of GOF and hypomorphic alleles. As @swamidass noted, _P53_ mutations are about 50/50, and I notice that you completely ignored the _G6PD_ ones. Why?

> [@The DI responds to my now--two-years-old review of ROTGH](https://discourse.peacefulscience.org/t/the-di-responds-to-my-now-two-years-old-review-of-rotgh/16709/36):
>
> There are studies that do the work no single or collection of cherrypicked studies do.

No. The reality is that no study can do all that work. All of them are limited in some way. The _in vitro_ ones are necessarily highly biased in favor of those proteins that are easier to purify. Guess what kind those are?

Collections of hypomorphic and GOF mutants are not limited in that way.

> [@The DI responds to my now--two-years-old review of ROTGH](https://discourse.peacefulscience.org/t/the-di-responds-to-my-now-two-years-old-review-of-rotgh/16709/36):
>
> Attempt to get a distribution of effects.

In what type of proteins? A specific type, no?

> [@The DI responds to my now--two-years-old review of ROTGH](https://discourse.peacefulscience.org/t/the-di-responds-to-my-now-two-years-old-review-of-rotgh/16709/36):
>
> They find that it’s a gaussian,

In what type of proteins? IDPs? What’s the antecedent of “it,” _ **precisely and literally** _?

> [@The DI responds to my now--two-years-old review of ROTGH](https://discourse.peacefulscience.org/t/the-di-responds-to-my-now-two-years-old-review-of-rotgh/16709/36):
>
> …with the mean substantially in the destabilizing.

Not for surface residues, for which the mean was basically 0. You are missing so much by trying to win arguments with this lame cherrypicking. You can’t even see it in the data you are presenting!

> [@The DI responds to my now--two-years-old review of ROTGH](https://discourse.peacefulscience.org/t/the-di-responds-to-my-now-two-years-old-review-of-rotgh/16709/36):
>
> I cite some of them in that thread, there are others that show the same.

I don’t know of any that are comprehensive. Certainly none you cited were.

> [@The DI responds to my now--two-years-old review of ROTGH](https://discourse.peacefulscience.org/t/the-di-responds-to-my-now-two-years-old-review-of-rotgh/16709/36):
>
> Why do I have to explain this? You should not need me to explain this. What the fork is going on?

Because you’re not explaining anything. You appear to be arguing for the sake of arguing, particularly obvious from your repeated straw men.

> [@The DI responds to my now--two-years-old review of ROTGH](https://discourse.peacefulscience.org/t/the-di-responds-to-my-now-two-years-old-review-of-rotgh/16709/37):
>
> On another note, what the hell blew up your irony meter?

See above.

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