Figure 1. Minimum action path trajectory of the TrpRS conformational cycle. Conformational transition states, or high energy barriers, occur along both the induced-fit and the subsequent catalytic transition. The TrpRS Urzyme is blue, the Connecting Peptide 1 insertion is green, and the anticodon-binding domain is wheat. The rate-limiting barrier occurs when aromatic rings in the D1 switch (red transparent surfaces) must rearrange.
Figure 4. Verge and Folio Escapement mechanism from a wooden clockwork. This mechanism is driven by a weight on a string that drives the rotation of the large gearbox. Rotation is limited, however, by the swing of the lever arm, whose period is tuned to tick off a second every time the escapement mechanism allows a slip. This is an example of the conversion of free energy into a metric for time (i.e. information).
Figure 3. High correlations between kinetics and structural changes with computational parameters validate all three characterizations of 15 combinatorial mutants of the D1 switching motif.
Figure 5. Cartoon of the interplay of domain motion and free energy in the tryptophan activation mechanism. Green dashed line indicates binding free energy; brown dashed line indicates conformational free energy. The active site is assembled transiently during the domain motion, so high-affinity transition-state affinity occurs only during the shaded portion.
Figure 2. Combinatorial point mutagenesis and modular thermodynamic cycles give quantitatively similar estimates of the energetic coupling, –5 kcal/mole, that enhances both catalysis and specificity. That coupling assures that catalysis and recognition occur if and only if domain motion occurs. That conditional catalysis is essential for efficient free energy coupling.