Role of wobble base pair geometry for codon degeneracy: purine-type bases at the anticodon wobble position

Codon degeneracy is a key feature of the genetic code, explained by Crick (J Mol Biol 19:548-555, 1966) in terms of imprecision of base pairing at the codon third position (the wobble position) of the codon-anticodon duplex. The Crick wobble rules define, but do not explain, which base pairs are allowed/disallowed at the wobble position of this duplex. This work examines whether the H-bonded configurations of solitary RNA base pairs can in themselves help decide which base pairs are allowed at the wobble position during codon-anticodon pairing. Taking the purine-type bases guanine, hypoxanthine, queuine and adenine as anticodon wobble bases, H-bonded pairing energies and optimized configurations of numerous RNA base pairs are calculated in gas and modeled aqueous phase at the B3LYP/6-31 G(d,p) level. Calculated descriptors of alignment of these solitary base pairs are able to screen between allowed and disallowed base pairs for all cases studied here, except two cases which invoke base-sugar interactions in the codon wobble nucleoside. The exclusion of adenine from the anticodon wobble position cannot be explained on the basis of pairing facility or base pair geometry. These DFT results thus account for the specificity and degeneracy of the genetic code for all cases involving guanine, hypoxanthine and queuine as anticodon wobble bases.