James Tour and his 60-day challenge

[Rumraket (Mikkel R.)]

@lee_merrill

In fact, why don’t you all refute Axe? There has been this long discussion of Axe’s paper, show me please one point that has gone unaddressed that you all have made, that has proven to be unanswerable.

Ahem, the series of posts that led to this one of mine did in fact accomplish what you are now pretending it didn’t, which you didn’t get back to:

Did Douglas Axe Disprove Evolution? Spoiler: No

But you acknowledge later on that more mutations result in more degradation of function, which I agree is fairly self-evident. That isn’t all I say on that topic, and I give reasons to think the relationship isn’t all that simple for protein function. But I think Axe’s argument is different, the wt enzyme is farther from functional collapse, not as close to it as the partially disabled enzyme he starts with. So then to remove the buffering effect, the wt enzyme is partially disabled. That’s exactly what we can’t just assume (reducing the capacity to buffer against the destabilizing effects of mutations doesn’t necessarily mean the enzyme the enzyme suffers loss of catalytic activity, these two factors can’t be directly interconverted), and why Axe needs to do activity assays. And it’s another reason for why the constraints on protein function don’t function in the way typos affect readability of a sentence. But I think this again is fairly self-evident, and also Axe gives de…

My challenge is unanswerable. I demonstrate with simple logic that if Axe’s own argument with sentence readability actually succeeds in undermining the claim that Axe should have tested the wild-type enzyme rather than a specifically constructed temperature sensitive variant, then that also undermines Axe’s own experiment as he carried it out in practice. In which case, by Axe’s own argument, Axe’s own experiment is invalid and the result can not be trusted.

You can’t have it both ways. You can’t both think that Axe’s response to objection 3 is valid AND that Axe’s own experiment was performed correctly.

Ultimately this comes back to @Art Hunt’s question to Axe about the request for a conversion factor between the two hills in his figures, which Axe never provides.

As in, we have been given no reason to think Axe has actually determined that the level of mutational sensitivity his enzyme exhibits in relation to the activity of the enzyme (which he doesn’t measure), is giving the correct fraction of functional serine beta-lactamase folds in protein sequence space.