Understanding the difference between necessity and sufficiency is supremely important in order to build solid arguments in science. While I am sure you all agree this to be the case, it is interesting how often we fall prey to fallacy if we disregard this fundamental distinction. Sadly, there are research projects that hinge on shaky grounds because it is often enticing to be selective about which parts of causal relationships to pursue and which to ignore. There are many examples I could quote, but none come close to the idea of enzyme mimicry, which is one of the most absurd and ludicrous notions. Time and again we see claims of simple systems that approach enzymatic efficiency. These ideas persist and, unless weeded out from the literature, confuse students who take sand castles for their face value. It happened with Atassi’s claims of cyclic peptide-based miniature enzymes in the 1990’s and it happened again more recently, when Ser-His was billed as an efficient catalyst with protease-like qualities. The truth is that the presence of catalytic groups in close proximity is necessary, but not sufficient for enzymatic activity. Stable and precise alignment of the said functionalities would make a catalyst, which is not achevable with small molecules. There is a nice recent Org. Lett. paper by Don Hilvert and Sam Gellman, which takes on Ser-His, goes through a number of control experiments, and delivers the lasting verdict (again): do not try to mimic enzymes.
Dear Andrei, be reminded that we are living in a post-truth era (in German: postfaktisch, post-facts). Borders of “science in fiction and fiction in science” are starting to blur quite heavily in these days. Therefore, it is eminent that some all-time-greats try to fix them. B
PS: Hope that south of Canada science will not get a k.o.
Ha! Indeed, very insightful. No one cares about fact checking anymore.
Dear Dr. Yudin,
It would seem to me that the problem with a catalyst like Ser-His is that it is too flexible, and thus that amide bond rotation would make it so that the predominant rotamer is a huge mix of all sorts of conformational angles. Thus, there is no “incentive” for this molecule to occupy he correct catalytic conformation.
Yet, I reckon the amide bond is important for function, so no question of changing the single bond to a double (rigid) bond somehow.
But it would seem not too difficult to me to anchor these two catalytic groups on a benzene ring scaffold sort of like EDTA. would it be feasible in your opinion?
I am afraid not, my friend. So much of this has been tried, to no avail.