Summary

Natural sequences are not the most stable sequences (1). Instead, they are approximately 1.8 kcal/mol less thermostable on average than the highest-fitness mutant.

See also

1.
Tsuboyama K, Dauparas J, Chen J, Laine E, Mohseni Behbahani Y, Weinstein JJ, et al. Mega-scale experimental analysis of protein folding stability in biology and design. Nature. 2023;620(7973):434–44. Available from: https://doi.org/10.1038/s41586-023-06328-6