## 1 Introduction  
The key component of protein synthesis is the ribosome, a macromolecular device formed by two subunits of distinct size composed of RNA (ribosomal RNA or rRNA) and proteins. This supramolecular structure mediates the steady addition of amino acids (aas), carried by the transfer RNAs (tRNAs), into the emerging protein chain via peptide bond formation. By virtue of the idiosyncratic arrangement of the small and large subunits, a \(\sim\)100 Angstroms (A) long chamber is formed in the inter-subunit space, which is used by the tRNAs to cross the entire ribosome in a coordinated manner as they bind the primary interaction slots called A (for aminoacyl), P (for peptidyl) and E (for exit) sites [1]. In this scenario, the tRNAs play as dynamic agents that facilitate the synergism among the small and large subunits. Indeed, the main steps of protein translation, _i.e._, initiation, aa-tRNA incorporation (decoding) and translocation are in essence coupled to the structure and dynamic behavior of tRNA molecules. The tRNA secondary structure is commonly displayed in a cloverleaf shape [2], in which distinct stems are stabilized by Watson-Crick base pairings: the anticodon stem loop or ASL (complementary to the messenger RNA, mRNA's codon), the D stem loop, the acceptor stem (which shows the conserved 3' terminal CCA sequence to which the aa has been linked by aminoacyl tRNA synthetases or aaRSs) and the T-arm, in addition to the extra loop (which is variable in size and not present in all tRNA species). Early X-ray structure determination of yeast tRNA\({}^{\text{Phe}}\) showed that tRNAs form a compact l-shaped molecule [3, 4, 5, 6]. In this l-shaped tertiary configuration, one extreme is formed by the acceptor stem and T-arm, whereas the distal part is formed by the D and anticodon stems (Figure 1a). As anticipated by [PERSON] [7], tRNA shape is directly correlated with its workings as the adaptor molecule during translation: The anticodon at one end reads the mRNA; the acceptor stem at the other end carries the cognate amino acid. Since the first crystallographic structures, a wealth of data has shown that tRNA molecules display a common global shape, the main difference between them being the angle formed by the two arms of the l-shaped structure (Figure 2). The increasing number of structures has also revealed variability in structural details to specifically interact with the corresponding maturation/modification enzymes or aaRSs. This is especially true in the case of some mitochondrial tRNAs for instance, which display unique structural features. Details notwithstanding, the prevalence of an identical architectural framework in all tRNAs, either canonical or divergent, in all three kingdoms of life is undeniable  
Figure 1: Tertiary structure and computational analysis of tRNA’s structural plasticity. **(a)** Color-coded B factor information, which can be described as flexibility estimation, is displayed for the phosphorus atoms of tRNA\({}^{\text{Asp}}\) X-ray structure (PDB 2 TRA) [8]; **(b)** Color-coded flexibility prediction by constraint counting for the same tRNA species, in which overconstrained regions are indicated in blue, rigid regions in green, and flexible regions in red. (Figure adapted from [9], Copyright 2008 Elsevier). (for an excellent review, see [10] and references therein). At the same time, tRNA molecules not only traverse the inter-subunit space during protein synthesis, but can also rearrange their L-shaped structure as the distortions of the tRNA molecule during its course of action are significant. Indeed, it is acknowledged that these reconfigurations are imperative during many stages of the protein translation elongation step. In this review, we will first summarize the contributions made by experimental (mainly kinetic and smFRET studies) and computational methods to our understanding of the variations in the structure of the tRNA when bound to the ribosome, giving a sense of its flexible nature.