 PLoS Comput Biol. Feb 2008; 4(2): e1000002. Published online
Feb 29, 2008. doi:  10.1371/journal.pcbi.1000002 PMCID:
PMC2265470  How Protein Stability and New Functions Trade Off
David Eisenberg, Editor   Numerous studies have noted that the
evolution of new enzymatic specificities is accompanied by loss
of the protein's thermodynamic stability (ΔΔG), thus suggesting
a tradeoff between the acquisition of new enzymatic functions
and stability. However, since most mutations are destabilizing
(ΔΔG>0), one should ask how destabilizing mutations that confer
new or altered enzymatic functions relative to all other
mutations are. We applied ΔΔG computations by FoldX to analyze
the effects of 548 mutations that arose from the directed
evolution of 22 different enzymes. The stability effects,
location, and type of function-altering mutations were compared
to ΔΔG changes arising from all possible point mutations in the
same enzymes. We found that mutations that modulate enzymatic
functions are mostly destabilizing (a