Evidence suggests that molecular interactions may evolve differently for proteins compared to functional RNA. We suggest that for RNA interacting with other nucleic acid molecules, the selection of higher affinity interactions leads to greater specificity, whereas for proteins interacting with other proteins, there is a trade-off between selection for greater affinity vs. greater specificity. This difference arises from the nature of the molecular contacts driving intra- and inter-molecular interactions, with crucial roles for non-specific hydrophobic interactions driving affinity in proteins and for specific hydrogen bonds driving affinity and specificity in RNA. The implications of this difference are discussed.
Liberles et al. (Mon,) studied this question.