As the enzyme moves through the transition state, catalytic residues must undergo extreme entropic loss to allow for efficient chemistry. However, the catalytic site scaffold can still access many states, potentially increasing its entropy, even in the transition state, reducing the entropic loss across the entire enzyme (teal). This contrasts with the scenario where the enzyme scaffold also loses entropy, increasing the entropic loss across the entire enzyme (orange). (B) The ribosome (large subunit-blue; small subunit-yellow, mRNA-pruple) goes through large conformation changes between the initiation state (GS1) and elongation state (GS2). The more conformations the ribosome can access (represented by the number of ribosome states and size the red arrows), the more conformational entropy exists during the transition from GS1 to GS2 or vice versa.