R
rossum
Guest
This is discussing evolution. Since every ancestor has to be functional enough to reproduce, then the assumption of random bases for the entire protein is incorrect. In any evolutionary process we know (not assume) that the protein is functional enough to allow the organism carrying it to survive long enough to reproduce. If the organism does not reproduce, then that particular protein configuration will not be carried on into the next generation. Evolution is an iterative process.Extrapolating from our data and from modest sequence constraints on interhelical turns (23, 28–30), we can estimate that if every position in the protein had been randomized, a library of ˜10^24 members would have been needed to obtain AroQ mutases. (colour added)
pnas.org/content/98/19/10596.full#ref-30
That is often the reason simple probability calculations are not useful in this area. It is much easier to calculate completely random probabilities, but in real life, the process of natural selection greatly constrains the range of possibilities that are actually found. Incorrect mathematical models lead to incorrect results.
Quoting further from your PNAS reference, this point is borne out:
reference:
Your own source is telling you that single step methods will not work, while “incremental strategies” “as in natural evolution” will succeed.Our estimate of the low frequency of protein catalysts in sequence space indicates that it will not be possible to isolate enzymes from unbiased random libraries in a single step. The required library sizes far exceed what is currently accessible by experiment, even with in vitro methods (31, 35). Instead, as in natural evolution, the design of new enzymes will require incremental strategies in which, for instance, a suitable scaffold is first generated, binding and catalytic groups are subsequently added, and the ensemble is optimized in an iterative fashion. Our two-stage approach to binary-patterned mutases and work on the redesign of existing enzymes (36–38) demonstrate the power of stepwise and modular procedures for directing the course of evolution.
You need to look at your own sources more thoroughly. Incremental, stepwise, strategies, such as evolution, require a different mathematical treatment from the single step “tornado in a junkyard” strategies, often used as strawmen by the ID side.
rossum