It has been demonstrated, experimentally and computationally, that vibrational circular dichroism (VCD) is capable of providing useful information on the base pair and sugar phosphate structures of nucleic acids and, therefore, can be used to solve structural problems. The dipole coupling mechanism has been further shown to dominate the nucleic acid VCD, particularly in the more isolated phosphate stretching region.
Characterization of a number of natural and model nucleic acids in both base stretching and phosphate stretching regions successfully correlates the spectral patterns to their compositions and conformations. A fairly strong dependence on the base sequence is evidenced in the VCD of the base deformation modes and little in the symmetric PO2- stretching modes, as expected. The handedness of nucleic acids is directly linked to the sense of the VCD couplets. This sensitivity of VCD has been used to unambiguously confirm the conformations of poly(dI-dC)poly(dI-dC) under low salt and high salt plus NiCl2.
The almost identical VCD spectra of rU*rArU, dT*dAdT and rU*dAdT also indicates a very similar base-pair structure for RNA, DNA and RNA-DNA hybrid triplexes of the same kind. The steric hindrance existing in the triple helical structure may be responsible for their similar optical properties. Nondegenerate extended coupled oscillator (NECO) calculations for rU*rArU oligomer were in better qualitative agreement with a reverse Hoogsteen base pairing scheme than with the expected Hoogsteen base pairing scheme.
An ordered poly(U) structure present at low temperature was found to be primarily an intermolecular double stranded helix under our sampling conditions. Addition of Mg2+ stabilized this ordered structure by raising the transition temperature. The VCD features of poly(U)*poly(U) were qualitatively explained with an asymmetric base pairing structure based from NECO calculations.