Iso-energetic multiple conformations of hypermodified nucleic acid base wybutine (yW) which occur at 37(th) position in anticodon loop of tRNA(Phe).

Conformational preferences of wybutine (yW) have been studied by quantum chemical semi-empirical Perturbative Configuration Interaction with Localized Orbitals (PCILO) and PM3 methods. Automated full geometry optimization by using RM1 along with ab-initio Hartree-Fock (HF-SCF) and Density Functional Theory (B3LYP/6-31G**) calculations have also been made to compare the salient features. Molecular dynamics (MD) simulation has been performed to see the solvation effect on wybutine side chain. The preferred conformations of wybutine side chain spreads away 'distal' from five membered imidazole moiety of tricyclic base. The intramolecular interactions provide stability to the preferred wybutine structure. The most stable and alternative stable structures obtained by PCILO and PM3 methods reveal that wybutine side chain may have multiple iso-energetic conformations. Molecular dynamics (MD) simulation study also confirms multiple conformations of wybutine side chain by showing regular periodical fluctuations over the 2 ns time period. These fluctuations occur when torsion angle α takes value ±90° and ±120° as observed in the most stable and alternative stable structures resulted by PCILO and PM3 methods. Such conformational behavior of wybutine may have certain implications on frameshifting to prevent extended Watson-Crick base pairing by maintaining proper codon-anticodon interactions during protein biosynthesis process.