ORIGINAL PAPER Conformational Preferences of Modified Nucleoside N 2 -methylguanosine (m 2 G) and Its Derivative N 2 , N 2 -dimethylguanosine (m 2 2 G) Occur at 26th Position (Hinge Region) in tRNA Rohit S. Bavi • Asmita D. Kamble • Navanath M. Kumbhar • Bajarang V. Kumbhar • Kailas D. Sonawane Published online: 7 July 2011 Ó Springer Science+Business Media, LLC 2011 Abstract Conformational preferences of the modified nucleosides N 2 -methylguanosine (m 2 G) and N 2 ,N 2 -dim- ethylguanosine (m 2 2 G) have been studied theoretically by using quantum chemical perturbative configuration inter- action with localized orbitals (PCILO) method. Automated complete geometry optimization using semiempirical quantum chemical RM1, along with ab initio molecular orbital Hartree–Fock (HF-SCF), and density functional theory (DFT) calculations has also been made to compare the salient features. Single-point energy calculation studies have been made on various models of m 2 G26:C/A/U44 and m 2 2 G26:C/A/U44. The glycosyl torsion angle prefers ‘‘syn’’ (v = 286°) conformation for m 2 G and m 2 2 G molecules. These conformations are stabilized by N(3)–HC2 0 and N(3)–HC3 0 by replacing weak interaction between O5 0 – HC(8). The N 2 -methyl substituent of (m 2 G26) prefers ‘‘proximal’’ or s-trans conformation. It may also prefer ‘‘distal’’ or s-cis conformation that allows base pairing with A/U44 instead of C at the hinge region. Thus, N 2 -methyl group of m 2 G may have energetically two stable s-trans m 2 G:C/A/U or s-cis m 2 G:A/U rotamers. This could be because of free rotations around C–N bond. Similarly, N 2 ,N 2 -dimethyl substituent of (m 2 2 G) prefers ‘‘distal’’ conformation that may allow base pairing with A/U instead of C at 44th position. Such orientations of m 2 G and m 2 2 G could play an important role in base-stacking interactions at the hinge region of tRNA during protein biosynthesis process. Keywords Transfer RNA Á Modified nucleosides Á m 2 G Á m 2 2 G Á PCILO Introduction Transfer RNA (tRNA) is the most extensively modified nucleic acid in the cell, and immediately after its discovery, it was shown that it contains modified nucleosides [1, 2]. These modified components present in tRNA are deriva- tives of the four common ribonucleosides. Most of the modifications involve simple alkylation, hydrogenation, thiolation, isomerization, and methylations of these four common ribonucleosides in the base and the 2 0 -hydroxyl group of the ribose. However, some modifications involve complex chemical modifications that are characterized by the presence of diverse functional groups in substituents, such tRNA components are referred as hypermodified nucleosides. These modified nucleosides are present at 34th ‘‘wobble’’ position and at 3 0 -adjacent (37th) position in the anticodon loop of tRNA from all domains of life [3–5]. The modifications present at 3 0 -adjacent position prevent extended Watson–Crick base pairing during protein bio- synthesis process, whereas the modifications present at 34th position may restrict or enlarge the scope of wobble base pairing [6–8]. Electronic supplementary material The online version of this article (doi:10.1007/s12013-011-9233-1) contains supplementary material, which is available to authorized users. R. S. Bavi Á A. D. Kamble Á B. V. Kumbhar Á K. D. Sonawane (&) Department of Biochemistry, Shivaji University, Kolhapur 416 004, M.S, India e-mail: kds_biochem@unishivaji.ac.in N. M. Kumbhar Department of Biotechnology, Shivaji University, Kolhapur 416 004, M.S, India K. D. Sonawane Department of Microbiology, Shivaji University, Kolhapur 416 004, M.S, India 123 Cell Biochem Biophys (2011) 61:507–521 DOI 10.1007/s12013-011-9233-1