Correlation between the backbone and side chain conformations in 5'-nucleotides. The concept of a 'rigid' nucleotide conformation

Abstract

Conformational energies of the 5'-adenosine monophosphate have been computed as a function of χ and ψ , of the torsion angles about the side-chain glycosyl C(1')-N(9) and of the main-chain exocyclic C(4')-C(5') bonds by considering nonbonded, torsion, and electrostatic interactions. The two primary modes of sugar puckering, namely, C(2')-endo and C(3')-endo have been considered. The results indicate that there is a striking correlation between the conformations about the side-chain glyocsyl bond and the backbone C(4')-C(5') bond of the nucleotide unit. It is found that the anti and the Gauche-Gauche (gg), conformations about the glycosyl and the C(4')-C(5') bonds, respectively, are energetically the most favored conformations for 5'-adenine nucleotide irrespective of whether the puckering of the ribose is C(2')-endo or C(3')-endo. Calculations have also shown that the other common 5'-pyrimidine nucleotides will show similar preferences for the glycosyl and C(4')-C(5') bond conformations. These results are in remarkable agreement with the concept of the "rigid" nucleotide unit that has been developed from available data on mononucleotides and dinucleoside monophosphates. It is found that the conformational 'rigidity' in 5'-nucleotides compared with that of nucleosides is a consequence of, predominantly, the coulombic interactions between the negatively charged phosphate group and the base. The above result permits one to consider polynucleotide conformations in terms of a "rigid" C(2')-endo or C(3')-endo nucleotide unit with the major conformational changes being brought about by rotations about the P-O bonds linking the internucleotide phosphorus atom. IT is predicted that the anti and the gg conformations about the glycosyl and the C(4')-C(5') bonds would be strongly preferred in the mononucleotide components of different purine and pyrimidine coenzymes and also in the nucleotide phosphates like adenodine di- and triphosphates.