There’s your ID hypothesis predicting again. If you disagree, name a single enzyme that you know (not guess) has a unique substrate. You were spectacularly wrong about beta-lactamase.
And as for neutral mutations, how do you explain these data?
Active barnase variants with completely random hydrophobic cores.
The central structural feature of natural proteins is a tightly packed and highly ordered hydrophobic core. If some measure of exquisite, native-like core packing is necessary for enzymatic function, this would constitute a significant obstacle to...