The catalytically-competent ensemble model also provides an energetic grounding for how conformational dynamics can be correlated with the evolvability of proteins. The relationship between increased conformational dynamics and evolvability is often discussed as altering the probability active sites conformational states , but it can extend to the energetic stabilization contributed by distal entropy in a catalytically competent ensemble. Promiscuous reactions, or errors, in catalysis are the first step towards evolutionary novelty and a broader conformational ensemble both locally in the active site and favored by distal conformational entropy can promote such reactions. Indeed, there is evidence for increased error rate for tRNA Met on the ribosome , which suggests that the entropically favoured transition state may also be broader at the active site. This model also provides a hypothesis for the contribution of some distal mutations accumulated in directed evolution experiments, especially for enzymes that change flexibility in regions beyond the active site . With this framework, the challenge is to quantify how conformational heterogeneity in the protein scaffold (or, in the case of the ribosome, rRNA scaffold), substrate, and solvent molecules alter the conformational ensemble in a way that affects both the equilibrium and the transition rates between different functional steps of a catalytic cycle.