Figure 6. Accuracy in rotameric systems.

For each of the four inhibitors, either in the unbound state (bottom row), or in the context of a rigid binding pocket (top row), we computed the exact marginal entropies for all combinations of 1–5 torsions, according to the Boltzmann distribution across the 5 × 10⁴ configurations representing each system. Using these exact marginal entropies we computed the MIST (blue lines) or MIE (red lines) approximations to the entropy (−TS°) of each system. The convergence as a function of approximation order is shown in comparison to the analytically determined entropy of the full system (dashed black line).