Analysis of action of the wobble adenine on codon reading within the ribosome.

Computer graphics simulation of the interaction between the codon-anticodon duplexes containing adenine in the first (wobble) position of the anticodons, and bound to the ribosomal A- and P-sites, was made. This demonstrated that widespread use of adenine in the wobble position in anticodons should lead to a low efficiency of ribosomal translation, since the wobble A of the P-site tRNA weakens the codon-dependent binding of aminoacyl-tRNA at the A-site via interduplex interaction. Besides the canonical partner U, the wobble A of aminoacyl-tRNA can recognize A, C, G in the third position of the codon by the formation of the propeller twist in the wobble pairs AA, AC, AG. The conversion of the wobble A into inosine improves its pairing with the codon bases (the pairs IA and IC, unlike AA and AC, should not form the propeller twist leading to the deformation of base-base hydrogen bonds) and should reduce an adverse effect of the P-site wobble adenine on the formation of the A-site duplex. The consequence of the interaction between the ribosomal P- and E-site duplexes has been formulated. According to this the E-site wobble A should enhance the probability of frameshifting. These properties of the wobble A and I could be a reason why A is very rarely observed in the first anticodon position and why evolutionary processes have developed the enzyme which modifies the wobble A to I. The results obtained can be subjected to direct experimental tests.