MD simulation studies to investigate iso-energetic conformational behaviour of modified nucleosides m(2)G and m(2) (2)G present in tRNA

Modified nucleic acid bases are most commonly found in tRNA. These may contain modifications from simple methylation to addition of bulky groups. Methylation of the four canonical nucleotide bases at a wide variety of positions is particularly prominent among the known modification. Methylation of N2 group of guanine is a relatively common modification in tRNA and rRNA. N2-methylguanosine (m(2)G) is the second most often encountered nucleoside in E. coli tRNAs. N2, N2- dimethylguanosine (m(2) (2)G) is found in the majority of eukaryotic tRNAs and involved in forming base pair interactions with adjacent bases. Hence, in order to understand the structural significance of these methylated nucleic acid bases we have carried out molecular dynamics simulation to see the salvation effect. The results obtained shows iso-energetic conformational behaviors for m(2)G and m(2) (2)G. The simulation trajectory of m(2)G shows regular periodical fluctuations suggesting that m(2)G is equally stable as either s-cis or s-trans rotamers. The two rotamers of m(2)G may interact canonically or non-canonically with opposite base as s-trans m(2)G26:C/A/U44 and s-cis m(2)G26:A/U44. The free rotations around the C-N bond could be the possible reason for these iso-energetic conformations. Dimethylation of G has almost no influence on base pairing with either A or U. Thus, these results reveal that modified nucleosides m(2)G and m(2) (2)G may play an important role to prevent tRNA from adopting the unusual mitochondrial like conformation.