Navanath M Kumbhar1, Bajarang V Kumbhar2, Kailas D Sonawane3
1Department of Biotechnology, Shivaji University, Kolhapur – 416 004, (M.S.), India.
2Structural Bioinformatics Unit, Department of Biochemistry, Shivaji University, Kolhapur -416 004, (M.S.), India.
3Structural Bioinformatics Unit, Department of Biochemistry and Microbiology, Shivaji University, Kolhapur – 416 004, (M.S.), India.
Transfer ribonucleic acids (tRNAs) are important molecules required in protein biosynthesis process. Instead of four common nucleosides tRNA also contains various modified (unusual) nucleosides. These modified nucleosides naturally occur in the anticodon loop of diverse tRNAs specific to various amino acids. Such modified nucleosides occur at the ‘Wobble’ (34th) and at the 3′- adjacent (37th) position in anticodon loop of tRNA. Modifications present at the 37th position may help define the proper reading frame for codon-anticodon interactions whereas modifications occur at the wobble position extend or restrict the selection of synonymous codons to be read by the tRNA. The hypermodified nucleoside N 6- hydroxynorvalylcarbamoyl adenosine, (hn6A) and its methylthio derivative 2-methylthio- N 6- hydroxynorvalylcarbamoyl adenosine, (ms 2 hn 6 A) occur at the 37th position in the anticodon loop of tRNA of thermophilic bacteria and archaea. Likewise, wybutosine is a tricyclic base and a member of the wyosine family of hyper modified guanosine found at the 3′-adjacent (37th) position in the anticodon loop of eukaryotic tRNA phe. Conformational preferences of various modified nucleosides have been studied by quantum chemical semi-empirical methods. Molecular dynamics (MD) simulation has also been performed to see the solvation effect on wybutine, hn 6 Ade, and ms 2 hn 6 Ade molecules. The preferred conformations of wybutine and N6-threonylcarbamolyl adenine side chain spreads away ‘distal’ from five membered imidazole moiety of base. Quantum chemical and molecular dynamics (MD) simulation studies reveal that wybutine side chain may have multiple iso-energetic conformations. Such conformational behavior of wybutine may have certain implications on frameshifting to prevent extended Watson- Crick base pairing by maintaining proper codon – anticodon interactions. Read More ..