“…The computational approaches have been often applied for enzyme stabilization when the constructed thermostable single- and multiple-point variants simultaneously exhibited increased activity at higher temperatures [46] , [47] . In the case of FGF protein stabilization, the computational design combining the energy-based and evolution-based calculations resulted in the protein variants where the enhanced melting temperature was positively correlated with prolonged bioactivity at 37 °C [26] , maintained mitogenic activity upon preincubation at elevated temperatures, and enhanced resistance towards proteolytic degradation [48] . This motivates us to apply such computational design also for the stabilization of FGF21.…”