Analysis of interactions between the codon-anticodon duplexes within the ribosome: their role in translation.

Computer graphics simulation of interactions between the codon-anticodon duplexes formed by normal elongator tRNAs at the ribosomal A, P and E-sites (the AP and PE interduplex interactions) was made. This demonstrated that only the correct duplexes at the A-site are compatible with the AP interduplex interaction. The selection of synonymous codons and anticodon wobble bases, together with the AP interduplex interaction, prevents frameshifting. In the absence of this interaction the efficiency of the selection falls off sharply. This suggests that the AP interduplex interaction should be retained during translocation and in the post-translocation state, i.e. the PE interduplex interaction that is identical with that of AP should exist to avoid frameshifting. In such a model the P-site duplex provides an indirect linkage between the A and E-site duplexes. The indirect linkage prohibits the simultaneous existence of the A and E-site duplexes. The wobble pairs of the P and E-site duplexes can affect the rate of the A-site occupation via the AP interduplex interaction and the AE interduplex indirect linkage. It is demonstrated that frameshifting can occur from the AP or PE codon-anticodon complex destabilization caused, for example, by small mobility of the wobble pairs, misreading of the codon, unmodified adenine and guanine at tRNA positions 34 (wobble) and 37, respectively. The results obtained can be subjected to direct experimental tests.