Conformational studies of nucleic acids. II. The conformational energetics of commonly occurring nucleosides

We have examined the conformational energetics of the eight most commonly occurring nucleosides--A, U, G, C, dA, dT, dG, dC--as monitored by a semi-empirical energy force field. These are the first reported calculations to completely explore the entire conformational spaces available to all eight major nucleosides using experimentally consistent furanose geometries and an appropriate force field. Central to our approach is the ability to model an experimentally reasonable furanose for each nucleoside directly from only one parameter, the phase angle of pseudorotation P, as described in the previous paper (D.A. Pearlman, and S.-H. Kim, preceeding paper in this issue). This allows us to specify the conformation of a nucleoside by three variables: torsion angle gamma (O5'-C5'-C4'-C3'); torsion angle chi (O4'-C1'-N9/N1-C4/C2); and P. In our study each of these parameters was allowed to vary independently and in small increments over the range 0-360 degrees. The empirically observed preferences for C3'-endo and C2'-endo sugar conformations, for anti and syn values of chi and for staggered (g+, t, g-) values of gamma can be explained on the basis of the energy maps so obtained. Finer details, such as the different conformational preferences of ribonucleosides and deoxyribonucleosides and of purines and pyrimidines, can also be extracted from these maps and are consistent with experiment. The calculations support previous descriptions of pseudorotation as hindered. Statistical Boltzmann population factors for different conformational ranges in gamma, chi, and P, as predicted by the calculations, are consistent with factors obtained from crystallographic data. The excellent results here provide additional support for the suitability of the new sugar modeling technique used.