Numerous researchers have employed elegant biochemical, biophysical, structural, genetic, and computational approaches to this problem, a few of which are highlighted here. For example, biochemical approaches have been employed to define the kinetic parameters governing every step of the elongation cycle, revealing that selection of the appropriate aminoacyl-tRNA (aa-tRNA) depends on a two step kinetic process [reviewed in (2) ]. Biophysical methods have revealed that conformational switching by rRNA and ribosomal protein L1 ensures exit of deacylated tRNA from the ribosome (1,3), while real time single molecule fluorescence and force measurements are revealing dynamic motions of the ribosome and tRNAs, and directly probing the forces stabilizing ribosomal complexes [reviewed in (4) ]. Biochemical, computational and high resolution structural methods have been employed to map changes in rRNA structures during the transit of tRNAs through the ribosome and during the peptidyltransfer reaction (5) (6) (7) (8) (9) (10) . Pertinent to this study, we have previously used a combination of molecular genetics, biochemical and biophysical approaches to identify the contributions of specific ribosomal proteins and rRNA bases involved in coordinating the stepwise process of accommodation of aa-tRNA into the ribosomal A-site, activation of the peptidyltransferase center, and recruitment of the trans-acting translocase (EF-G in bacteria, eEF2 in eukaryotes) using yeast ribosomes as a model (11) (12) (13) (14) (15) (16) .