QUANTUM CHEMICAL STUDY TO INVESTIGATE THE EFFECTS OF 5′-3′ DIPHOSPHATE BACKBONE ON THE CONFORMATION OF HYPERMODIFIED NUCLEOTIDE LYSIDINE (K2C) OCCUR AT WOBBLE (34TH) POSITION IN THE ANTICODON LOOP OF TRNAILE

Conformational preferences of hypermodified nucleotide ‘lysidine’ in the model diphosphate (Me-p-k2Cp-Me) segment of anticodon loop of tRNAIle have been studied by using quantum chemical perturbativeconfiguration interaction with localized orbitals (PCILO) method. The consequences of 5′-3′ diphosphate backboneon the conformation of zwitterionic, non-zwitterionic, neutral and tautomeric forms of lysidine have beeninvestigated and compared with diphosphate backbone of cytidine nucleotide. Automated geometry optimizationusing semi-empirical quantum chemical RM1, quantum mechanical Hartree-Fock (HF-SCF) and DensityFunctional Theory (B3LYP/6-31G**) calculations have also been made to compare the salient features. Theorientation of lysine moiety is found trans to the N(1) of cytidine in the predicted most stable conformations of allthe four forms of lysidine in the model 5′-3′ diphosphate anticodon loop segment. The lysine substituent folds backand form hydrogen bond with 2′-hydroxyl group of ribose sugar. Lysine substituent of various diphosphate lysidinenucleotides does not interact with 5′or 3′ diphosphate backbone. All forms of lysidine nucleotides retain anti (χ=3 )glycosyl (glycosidic) torsion angle. Diphosphate cytidine nucleotide prefers (χ=33 ), which could destabilize thec3′-endo sugar to the minor extent. The interaction between O(12b)----HO2′ of tautomer diphosphate nucleotidemay help in maintaining the c3′-endo sugar puckering at wobble (34th) position as compared to other lysidineforms and cytidine nucleotide. Hence, tautomeric form of lysidine along with suitable hydrogen bond donoracceptorgroups may also provide structural stability for the proper recognition of AUA codons instead of AUGcodons.