You fried my irony meter there.
Let’s. Just to be clear, I didn’t do it personally. I supervised the postdoc and students who did the hands-on work.
I didn’t. I was very clear about that in the very thread you linked to above:
LOL. Was that not clear, Mikkel?
I cited our work because finding 8 of 8 disease-causing mutations increasing stability was unremarkable.
Active-site changes that decrease function pretty consistently increase stability. We’ve known this for a very long time. One old example:
https://www.pnas.org/doi/epdf/10.1073/pnas.92.2.452
For large collections of hypomorphic alleles (for example G6PD, because deficiency protects against malaria), there appear to be groupings with differing relationships between stability and function:
https://www.cell.com/cell-reports/fulltext/S2211-1247(17)30246-2
And it’s not limited to mutations. You can do a control PCR reaction to measure the activity vs. stability of Taq DNApol at different temperatures in an afternoon. Stabilizing the most abundant family of proteins in your body, the collagens, by glycation caused by excess glucose causes enormous human suffering in people with diabetes.