Continuing the discussion from Gauger and Mercer: Bifunctional Proteins and Protein Sequence Space:
Dr @Agauger -
I apologize that I could not raise this question directly in the “Bifunctional Proteins” thread due to my “noob” status. Hopefully I will gain enough site cred soon. Help my by liking my post, if you think it’s worth it!
You cited Tokuriki 2009 in the other thread to provide data on the question of a protein’s tolerance for mutations. Tokuriki’s key finding is that the loss of functionality increases exponentially with the number of mutations.
My recollection of Axe 2004 (please correct me if I am misremembering) is that Axe introduced several mutations that weakened the enzyme’s functionality before beginning the measurement of effects of further mutations on proteins.
Since the effects of mutations are exponentially worse for Axe’s crippled protein than for “normal” proteins, it would seem inappropriate to project Axe’s findings onto the state space for normal proteins. Does that make sense?
Of course, Tokuriki’s paper came 5 years after Axe’s, so I would not want to criticize Axe’s research on that basis. However, it would seem highly pertinent to scientific discussions from 2009 onward.
I would appreciate your thoughts on the matter whenever you have time.