Figure 1. Likelihood of contact between triplets (orange *, red o) and pairs (blue □, green ∇) of residue positions vs. the coevolution rank.

High MI triplets are likely to be in contact for triplets of residue positions (similar to coevolution seen in protein position pairs [5]), but doublets are not. For example, 40% of the top 5 highest ranking MI triplets are in contact, while only 20% of the top 5 highest ranking MI doublets are in contact. MI between RNA and polar amino acids, more likely to lie on the surface on the protein and therefore interact with RNA, enhances the trend (o triplets, ∇ doublets). High MI triplets between polar amino acids and RNA are most likely to be in contact. In comparison, random coevolution between pairs of amino acids is expected to have a contact frequency of 8% [5].