While we evidenced here a clearly favored reaction pathway from one of the conformational basins, it would be interesting to investigate in future work whether such a rich conformational landscape, relevant for reactivity, is pertinent for other RNases. The existence of distinct reaction pathways associated with different conformations paints a picture of enzyme catalysis much more complex than the traditional view. In cases of competing reaction routes with similar barriers, such effects may be key to rationalize reactivity, understand mutation effects, and predict activity changes, for instance in the context of enzyme design.