Structural Significance of Conformational Preferences and Ribose-Ring-Puckering of Hyper Modified Nucleotide 5'-Monophosphate 2-Methylthio Cyclic N 6 -Threonylcarbamoyladenosine (p-ms 2 ct 6 A) Present at 37th Position in Anticodon Loop of tRNA Lys .

Structural significance of conformational preferences and ribose ring puckering of newly discovered hyper modified nucleotide, 5'-monophosphate 2-methylthio cyclic N 6 -threonylcarbamoyladenosine (p-ms 2 ct 6 A) have been investigated using quantum chemical semi-empirical RM1 and molecular dynamics simulation techniques. Automated geometry optimization of most stable structure of p-ms 2 ct 6 A has also been carried out with the help of abinitio (HF SCF, DFT) as well as semi empirical quantum chemical (RM1, AM1, PM3, and PM6) methods. Most stable structure of p-ms 2 ct 6 A is stabilized by intramolecular interactions between N(3)…HC(2'), N(1)…HC(16), O(13)…HC(15), and O(13)…HO(14). The torsion angles alpha (α) and beta (β) show the significant characteristic patterns with the involvement of intramolecular hydrogen bonding to provide stability to the p-ms 2 ct 6 A. Further, molecular dynamics simulations of p-ms 2 ct 6 A revealed the role of ribose sugar ring puckering i.e. C2'-endo and C3'-endo on the structural dynamics of ms 2 ct 6 A side chain. The modified nucleotide p-ms 2 ct 6 A periodically prefers both the C2'-endo and C3'-endo sugar with 'anti' and 'syn' conformations. This property of p-ms 2 ct 6 A could be useful to recognize the starting ANN codons. All atom explicit MD simulation of anticodon loop (ACL) of tRNA Lys of Bacillus subtilis containing ms 2 ct 6 A at 37th position showed the U-turn feature, base stacking ability with other adjacent bases and hydrogen bonding interactions similar to the isolated base p-ms 2 ct 6 A. The ribose sugar puckering contributes to the orientation of the side chain conformation of p-ms 2 ct 6 A. Thus, the present study could be helpful to understand the structure-function relationship of the hypermodified nucleoside, ms 2 ct 6 A in recognition of the proper codons AAA/AAG during protein biosynthesis.