The ribosome is a complex molecular machine that, in order to synthesize proteins during the translation process, has to decode mRNAs by pairing their codons with matching tRNAs. Decoding is a major determinant of fitness and requires accurate and fast selection of correct tRNAs among many similar competitors. One must have in mind that most binding events are by non-matching (“non-cognate”) tRNAs and the ribosome needs to reject those as fast as possible in order to vacate the binding site. At the same time, the ribosome should keep the matching tRNAs bound long enough to allow the protein synthesis process ensue. Despite the importance of tRNA decoding, it was unclear until recently whether the modern ribosome, and in particular its large conformational changes during decoding, are the outcome of adaptation to its task as a decoder or the result of other constraints. Recent study
derived the energy landscape that provides optimal discrimination between competing tRNA substrates, and thereby optimal tRNA decoding. The optimal landscape is a symmetric one (see image). The study shows that the measured landscape of the prokaryotic ribosome is indeed symmetric. This model suggests that conformational changes of the ribosome and tRNA during decoding are means to obtain such an optimal tRNA decoder. The fact that both homologous recombination and tRNA decoding utilize conformational proofreading suggests that this is a generic mechanism that may be utilized broadly by molecular recognition systems.