The study explores the relationship between protein stability and evolvability, suggesting that more stable proteins are more evolvable. Using simulations with model lattice proteins and experimental mutations of cytochrome P450 BM3 variants, the researchers found that extra stability allows proteins to tolerate a wider range of beneficial mutations while maintaining their native structure. This increased robustness to mutations enhances the rate of functional innovation and the number of improved mutants. The findings highlight the importance of protein stability in natural evolution and provide insights into protein engineering strategies.The study explores the relationship between protein stability and evolvability, suggesting that more stable proteins are more evolvable. Using simulations with model lattice proteins and experimental mutations of cytochrome P450 BM3 variants, the researchers found that extra stability allows proteins to tolerate a wider range of beneficial mutations while maintaining their native structure. This increased robustness to mutations enhances the rate of functional innovation and the number of improved mutants. The findings highlight the importance of protein stability in natural evolution and provide insights into protein engineering strategies.