Possible relevance of mass, β-branching, and carboxylates to the operational RNA code (adapted from [56]). For ancient β-hairpins to interact with double-stranded RNA as envisioned by Carter and Kraut [1], large side chains would necessarily have faced away from the RNA minor groove. β-branched side chains on either face (re-entrant angles; green; threonine, valine on the inward face; isoleucine on the outer face) enhance β-structure formation. Carboxylate side chains in outward facing positions (red) could enhance solubility [58,59] and coordinate catalytic divalent metals, either for catalysis or to protect against RNA degradation [60].