Compare the series under the same assumptions
Single-geometry calculations offer a useful reference. The ensemble approach asks whether the relative rates change across conformers and how weighting those conformers affects the ranking. Consistent methods and convergence checks matter as much as the apparent difference between candidates.
A relative ranking with a defined scope
The toolkit contains barrier and rate-calibration methods for computational investigation. Constrained energy scans need further checks before they can be interpreted as verified transition states. A stable ranking does not by itself establish absolute reaction rates.
Connect accessibility to reactivity carefully
Ensemble ligandability can identify conformations worth examining; reaction calculations can ask what chemistry they support. That connection requires compatible structures and weights. It should be tested as a composition rather than assumed from the two methods’ availability.
- Boltzmann ensemble ligandability · Examine joint access and cysteine-chemistry questions. Boltzmann ensemble ligandability
- Local pKa design · Investigate an electrostatic change that could affect the reaction. Local pKa design
Choose the experiment that calibrates the ranking
Use a defined chemical series with measured reaction rates. Check whether the ranking survives plausible sampling and method changes before making it the basis for a larger synthesis campaign.