Conformational Preferences of Modified Nucleoside 5-Taurinomethyluridine, [tau]m^sup 5^U Occur at 'wobble' 34th Position in the Anticodon Loop of tRNA

Conformational preferences of hypermodified nucleoside 5-taurinomethyluridine 5'-monophoshate 'p-[tau]m^sup 5^U' (-CH2-NH2 ^sup +^-CH2-CH2-SO3 ^sup -^) have been investigated using semi-empirical RM1 method. Automated geometry optimization using ab initio molecular orbital HF-SCF (6-31G**) and DFT (B3LYP/6-31G**) calculations have also been made to compare the salient features. The RM1 preferred most stable conformation of 'p-[tau]m^sup 5^U' has been stabilized by hydrogen bonding interactions between O(11a)...HN(8), O1P^sub (34)^...HN(8), and O1P^sub (34)^...HC(10). Another conformational study of 5-taurinomethyluridine side chain has also been performed in context of anticodon loop bases of E. coli tRNA^sup Leu^. The atom O(11a) of [tau]m^sup 5^U^sub (34)^ side chain interacts with adenosine (A^sub 35^) as well as ribose-phosphate backbone which might provide structural stability to the anticodon loop. The glycosyl torsion angle of [tau]m^sup 5^U retains 'anti'-conformation. The solvent accessible surface area calculations revealed the role of [tau]m^sup 5^U in tRNA^sup Leu^ anticodon loop. MD simulation results are found in agreement with RM1 preferred stable structure. The MEPs calculations of [tau]m^sup 5^U^sub (34)^:G^sub 3^ model show unique potential tunnels between the hydrogen bond donor and acceptor atoms as compared to [tau]m^sup 5^U^sub (34)^:A^sub 3^ model. Thus, these results could pave the way to understand the role of [tau]m^sup 5^U^sub (34)^ to recognize UUG/UUA codons at atomic level in the mitochondrial disease, MELAS.