Conformational Preferences of Modified Nucleoside N^sup 2^-methylguanosine (m^sup 2^G) and Its Derivative N^sup 2^, N^sup 2^-dimethylguanosine (m^sub 2^^sup 2^G) Occur at 26th Position (Hinge Region) in tRNA

Conformational preferences of the modified nucleosides N^sup 2^-methylguanosine (m^sup 2^G) and N^sup 2^, N^sup 2^-dimethylguanosine (m^sub 2^^sup 2^G) have been studied theoretically by using quantum chemical perturbative configuration interaction 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^sup 2^G26:C/A/U44 and m^sub 2^^sup 2^G26:C/A/U44. The glycosyl torsion angle prefers "syn" (χ = 286°) conformation for m^sup 2^G and m^sub 2^^sup 2^G molecules. These conformations are stabilized by N(3)-HC2' and N(3)-HC3' by replacing weak interaction between O5'-HC(8). The N^sup 2^-methyl substituent of (m^sup 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^sup 2^-methyl group of m^sup 2^G may have energetically two stable s-trans m^sup 2^G:C/A/U or s-cis m^sup 2^G:A/U rotamers. This could be because of free rotations around C-N bond. Similarly, N^sup 2^, N^sup 2^-dimethyl substituent of (m^sub 2^^sup 2^G) prefers "distal" conformation that may allow base pairing with A/U instead of C at 44th position. Such orientations of m^sup 2^G and m^sub 2^^sup 2^G could play an important role in base-stacking interactions at the hinge region of tRNA during protein biosynthesis process.[PUBLICATION ABSTRACT]