How does your experiment demonstrate this? It’s possible to have many different sequences encode proteins that fold into nearly identical folds, and have the same catalytic activity. They can differ substantially in sequence. Beta-lactamases for example. Changing one amino acid in myosin is nothing to that. Compared to the whole sea of possible sequences, that particular beta-lactamase activity was very rare, even though there are probably tens of thousands (or more) of sequences that can carry out the function. It’s the proportion between total possible sequences of a given length, and the number of them that perform a particular function that matter. That’s what Doug was measuring.
I’d like to recommend a paper by Doug Axe.
Axe DD (2010) The case against a Darwinian origin of protein folds. BIO-Complexity 2010(1):1-12. doi:10.5048/BIO-C.2010.1
I’ll quote here the section I think is relevant.
The proportion of protein sequences that perform specified functions.
One study focused on the AroQ-type chorismate mutase,
which is formed by the symmetrical association of two identical
93-residue chains . These relatively small chains form a very
simple folded structure (Figure 5A). The other study examined
a 153-residue section of a 263-residue beta-lactamase . That
section forms a compact structural component known as a domain
within the folded structure of the whole beta-lactamase (Figure
5B). Compared to the chorismate mutase, this beta-lactamase domain
has both larger size and a more complex fold structure.
In both studies, large sets of extensively mutated genes were
produced and tested. By placing suitable restrictions on the allowed
mutations and counting the proportion of working genes
that result, it was possible to estimate the expected prevalence of
working sequences for the hypothetical case where those restrictions
are lifted. In that way, prevalence values far too low to be
measured directly were estimated with reasonable confidence.
The results allow the average fraction of sampled amino acid
substitutions that are functionally acceptable at a single amino
acid position to be calculated. By raising this fraction to the power
ℓ, it is possible to estimate the overall fraction of working sequences
expected when ℓ positions are simultaneously substituted
(see reference 25 for details). Applying this approach to the data
from the chorismate mutase and the beta-lactamase experiments
gives a range of values (bracketed by the two cases) for the prevalence
of protein sequences that perform a specified function. The
reported range  is one in 10^77 (based on data from the more
complex beta-lactamase fold; ℓ = 153) to one in 10^53 (based on
the data from the simpler chorismate mutase fold, adjusted to the
same length: ℓ = 153). As remarkable as these figures are, particularly
when interpreted as probabilities, they were not without
precedent when reported [21, 22]. Rather, they strengthened an
existing case for thinking that even very simple protein folds can
place very severe constraints on sequence.
Rescaling the figures to reflect a more typical chain length of
300 residues gives a prevalence range of one in 10^151 to one in
10^104. On the one hand, this range confirms the very highly many-to-
one mapping of sequences to functions. The corresponding
range of m values is 10^239 (=20^300/10^151) to 10^286 (=20^300/10104),
meaning that vast numbers of viable sequence possibilities exist
for each protein function. But on the other hand it appears that
these functional sequences are nowhere near as common as they
would have to be in order for the sampling problem to be dismissed.
The shortfall is itself a staggering figure—some 80 to 127
orders of magnitude (comparing the above prevalence range to
the cutoff value of 1 in 5×10^23). So it appears that even when m
is taken into account, protein sequences that perform particular
functions are far too rare to be found by random sampling.
Sorry, you’ll have to look at the original to get the exponents and references right.
When I spoke of promiscuous enzymes I was not referring to myosin, but to the many cases in the literature where promiscuous enzymes have been pushed to favor one substrate over another. Sometimes this can be done by directed evolution, for example.
In your example, you made a single change to the binding pocket that allowed a modified substrate to bind. That’s got nothing to do with promiscuity. I guess I was trying to be general. I agree, my failure to read carefully was in part due to my prejudices, as you call them. Not a good thing, but I have already apologized, and I am certainly not the first scientist to do so.