B−Z Conformational Transition of DNA Monitored by Vibrational Circular Dichroism. Ab Initio Interpretation of the Experiment

Abstract

The B−Z conformational transition was induced by Mn2+ ions in a synthetic oligonucleotide (dG-dC)20 and monitored by the vibrational circular dichroism (VCD). For the first time, the spectra were analyzed on the basis of quantum-mechanical computations. Force field and intensity tensors computed ab initio for smaller DNA fragments were transferred to a d(GCGCGCGC)2 octamer model including explicit water molecules. The method allowed us to assign and explain most of the frequency and intensity features observed in the absorption and VCD spectra of the B- and Z-forms. Particularly, the computations reproduced the VCD sign flip caused by the transition due to the CO stretching and allowed us to assign most spectral bands in the nitrogen bases vibrational region. Also, known isotopic effects (deuteration and a 18O substitution) were reproduced correctly. For the sugar−phosphate modes, the assignment of the VCD bands was hindered by a weak experimental signal. The approach based on quantum-mechanical computations was found superior to previous models based on coupled oscillator theory. Water molecules hydrogen-bonded to the DNA skeleton had to be included for reliable interpretation of the VCD and IR spectral patterns, namely, for the sugar−phosphate vibrations.