 systems biology can provide valuable insights into evolution by examining how protein structures, folds, and functions are linked to their fitness. This connection has been difficult to establish, however, due to the difficulty of directly observing the effects of misfolding on disease progression. The researchers then developed a fitness function based on in vitro measurements of enzyme activity, reversible and irreversible unfolding, and the physiological context, which accurately predicted the in vivo evolutionary outcomes of the population. This study demonstrates the importance of protein folding and stability in the evolution of successful organisms. This article was authored by Matthew Ipena, Melia Davliva, Matthew R. Bennett and others.