Comparative Structural Dynamics of tRNA Phe with Respect to Hinge Region Methylated Guanosine: A Computational Approach

Transfer RNAs (tRNAs) contain various uniquely modified nucleosides thought to be useful for maintaining the structural stability of tRNAs. However, their significance for upholding the tRNA structure has not been investigated in detail at the atomic level. In this study, molecular dynamic simulations have been performed to assess the effects of methylated nucleic acid bases, N 2 -methylguanosine (m 2 G) and N 2 - N 2 -dimethylguanosine (m 2 2 G) at position 26, i.e., the hinge region of E. coli tRNA Phe on its structure and dynamics. The results revealed that tRNA Phe having unmodified guanosine in the hinge region (G26) shows structural rearrangement in the core of the molecule, resulting in lack of base stacking interactions, U-turn feature of the anticodon loop, and TΨC loop. We show that in the presence of the unmodified guanosine, the overall fold of tRNA Phe is essentially not the same as that of m 2 G26 and m 2 2 G26 containing tRNA Phe . This structural rearrangement arises due to intrinsic factors associated with the weak hydrogen-bonding patterns observed in the base triples of the tRNA Phe molecule. The m 2 G26 and m 2 2 G26 containing tRNA Phe retain proper three-dimensional fold through tertiary interactions. Single-point energy and molecular electrostatics potential calculation studies confirmed the structural significance of tRNAs containing m 2 G26 and m 2 2 G26 compared to tRNA with normal G26, showing that the mono-methylated (m 2 G26) and dimethylated (m 2 2 G26) modifications are required to provide structural stability not only in the hinge region but also in the other parts of tRNA Phe . Thus, the present study allows us to better understand the effects of modified nucleosides and ionic environment on tRNA folding.