Gauger and Mercer: Bifunctional Proteins and Protein Sequence Space

[Agauger (Ann Gauger)]

@Mercer @T_aquaticus

@Mercer

Except that is not what Axe measured. What Axe measured is the probability of a few amino acid changes resulting in specific beta-lactamase activity when starting with a specific protein. This can’t be used to find the entire functional space for beta-lactamases, and it certainly can’t be used to find the total space of functional proteins. In fact, using the methods used by Axe to define function we would have to conclude that no human proteins have function because none of them break down beta-lactam antibiotics.

Exactly.

Dr. Gauger seems to have this bizarre idea of scientific discussions, in which two sides only cite the papers they think support their position.

Now, I propose that we discuss the relevance of our work, in which we rigorously measured enzymatic activity (and for fun the irony that we were intelligent designers) to Dr. Gauger’s global claims quoted twice above.

@T_aquaticus

I don’t think you have understood Axe’s paper.That’s the most charitable I can be: you either don’t understand or are mischaracterizing. Your last sentence makes it clear. Axe estimates the prevalence of sequences that adopt a specific functional fold; he doesn’t expect every protein to be a beta lactamase. You must know that.

In his experimental case he used a particular beta lactamase and calculated the proportion of possible sequences with that fold that could carry out that function. He then went on to generalize, making use of 2 studies with similar approaches, namely the use of mutagenesis to determine what proportion of sequences can carry out that fold’s function after mutagenesis. His paper was an estimate–it says so in the title. The methodology of the paper and its results were deemed worthy to be published in MBE.

@Mercer
Were there other studies using similar approaches back in 2004? I don’t know. Do you? And it wasn’t my paper.