Conformational studies of trinucleoside bisphosphates. 2. Potential energy calculations

Semi-empirical potential energy calculations were carried out for the conformations of ApApA, a trinucleoside bisphosphate (trimer), as proposed in the preceding paper in this journal. Energy minimals were obtained for these conformers, i. e. conformers I-I, I-II, III-I' and I'-I' (the first Roman numeral represents the conformation of the ApAp- moiety and the second one the -pApA moiety of ApApA), of the nearest-neighbor interactions, and conformers B1, B2 and B3 of bulged structures. The results show that the detailed conformations of the component dinuclotide (dimer) moieties in I-I, I-II, III-I' and I'-I' are close (+/- 10 degrees) to the corresponding stable conformations of dinucleotides in solution proposed by Lee and coworkers. The bulged conformations B1, B2 and B3 have open forms for each dinucleotide moiety. Their preferred local conformations are anti, gamma +, beta +, epsilon + (except for Ap- in B3, epsilon-), and 3' endo (except for Ap- in B3, 2' endo) for the glycosidic bond, C4'-C5', C5'-O5', C3'-O3' and the ribose moiety, respectively. The conformation of the phosphodiester linkage in -pApA moiety is zeta t2, alpha t3 for all the three bulged conformers, while that in ApAp- is zeta- 1, alpha t2 for B1, zeta+ 1 alpha- 2 for B2, and zeta+ 1, alpha+ 2 for B3. The calculated composite chemical shifts of the base protons from ring-current effects agree with the corresponding observed trimerization shifts. Conformers I-I and I'-I' are helix-like structures and correspond to the right-handed and the 'vertical-stacked' helices, respectively. The structure of I-II is similar to that observed in the ApApA single crystals. The bulged conformations may serve as models for frameshift mutations.