You have consistently not engaged in a dialog with me. You have repeatedly refused to read what I say or answer my questions, which are relevant, and you then make non sequiturs, or move the goal posts yourself.
I have told you why I think your myosin experiment is not relevant. I will say it again. The change you made was to one amino acid. Did it change the myosin’s catalytic behavior, such that it carried out a substantially different chemical reaction? No.
To put it in the simplest terms possible, the wild-type Myo1c simply doesn’t notice N6(2-methylbutyl)ADP, nor N6(2-methylbutyl) ATP. The Y61G mutant does all the things that wild-type does with ADP and ATP with the N6(2-methylbutyl) analogs. How is that not a new activity?
Did it change the enzyme’s reaction type? For example, did it go from being an aminotransferase to an aminotransferase plus decarboxylase? No. It hydrolyzes ATP in the absence of the modified ADP, just as before. Your wild type myosin doesn’t interact with the modified ADP. Your mutant myosin does. The modified ADP causes the mutant myosin to freeze on actin. That’s new behavior, sure. But it’s because the myosin mutant, in the presence of the modified ADP, can’t complete the ATP hydrolysis.
Let’s try again. What does your work show about my two premises:
- How easy functional sequences are to find;
They are still not easy to find. Your example does not meet the criterion of a genuinely new chemistry, involving a different reaction type, which I have explained, to no avail.
- how clustered functional sequences are together?
In your case they are right next door, and they are functional. They just aren’t genuinely new chemistry, involving a different reaction type, which I have explained, to no avail.
I could say something rude here, but I won’t. I have answered you more than once why I think your paper does not bear on what I have said. You are entitled to disagree. But I have no reason to continue.