Effect of a pH change on the conformational stability of the modified nucleotide queuosine monophosphate

The naturally occurring modified nucleotide queuosine 5'-monophosphate (QMP) related to biochemical regulatory pathways in the cell was investigated using quantum chemical approaches. The relative stability of biologically relevant conformations of QMP in solvent under a pH change was predicted at the BVP86/TZVP and MP2/TZVP levels of theory. Hydrogen bonding in QMP was studied using Bader's approach. The acidity constants of QMP were estimated using the COSMO-RS theory. It has been found that the neutral and anionic forms of QMP are the most stable in the physiological pH range. These forms correspond to the anti/north conformation and exist as zwitterionic tautomers having a negatively charged phosphate group (-1 for neutral and -2 for anionic) and a positively charged secondary amine group in the side chain. It was also found that QMP possesses the syn conformation in the cationic state at pH < 5.0 and undergoes syn to anti conformation transition when the pH increases, remaining in the anti conformation at the higher pH values. The marker IR bands specific for the anionic and neutral QMP forms in the 2300-2700 cm(-1) region were assigned to H-bonded NH groups of the QMP side chain. The bands between 800 and 1300 cm(-1) of the "fingerprint" (400-1500 cm(-1)) region were assigned to the vibrations of the ribose ring, the phosphate group and the side chain of QMP. The predicted IR spectra can be useful for the assignment of vibration bands in the experiential spectra of QMP or identification of the QMP forms. The revealed peculiarities of the QMP conformation sensitivity to a pH change as well as additional formed H-bonds could be responsible for specific nucleotide interactions with enzymes.