Computational prediction of vibrational spectra of normal and modified DNA nucleobases

Abstract

Purines, pyrimidines, and the corresponding ribose monophosphates are ubiquitous biomolecules involved in several cellular processes-in DNA and RNA, signaling, and energy transactions. In the new and exciting field of DNA-inspired nanostructures, they are used as fundamental building blocks. Unique features of the nucleobases are that several tautomeric states are close in energy and the tautomeric equilibria are sensitive to exocyclic substitution and pH. Knowing the exact structure and tautomer(s) at physiological conditions is crucial to understand the substrate specificities and catalytic mechanisms of the many enzymes for which these nucleobases are substrates. Very few spectroscopic methods can distinguish between tautomers and provide solution structures. Vibrational spectroscopy has long been known to be an excellent tool to obtain reliable information on nucleic acids. However, even when good-quality spectra are available, isotope editing is required to make reliable band assignments and identify structures unequivocally. Density functional theoretical (DFT) methods have become indispensible in assisting the assignment of observed spectra to normal modes, identification of tautomers, and modeling of spectra of isotope-edited molecules. We review the performance of DFT methods in the prediction of nucleobases and their analogs. We find that even with modest basis sets, trends in vibrational spectra can be predicted adequately and guide assignments to normal modes of the molecule. Shifts in band positions induced upon isotope labeling are reproduced more reliably than the band positions. Scaling considerably improves the agreement between the computed and experimental spectra, but accurate prediction of vibrations of exocyclic groups like C O requires that solvent effects are taken into account.

Raman spectral study of metal–cytosine complexes: A density functional theoretical (DFT) approach

“…Although the vibrational spectra of cytosine in various states have been studied by a lot of literatures [36,37,[42][43][44][45], there are little discrepancies in the assignments and wavenumber values of bands in the region 1400-1700 cm −1 , where most of the changes in the SERS spectra occur (see next section). Specifically, the peak observed at 1691 and 1641 cm −1 in the solid state and water solution is reproduced respectively at 1757 and 1637 cm −1 in gas state and water solvent by using PCM.…”

“…It is known that the C O stretching mode is the most inaccurately reproduced band in several molecules, and the solvent effects must be taken into account in order to accurately predict the vibrational spectra of exocyclic groups like C O [45]. When the cytosine molecule is simulated in water solvent by using PCM, it is produced at 1637 cm −1 , however, it is predicted to couple together with the Table 3 Calculated vibrational frequencies of the M-cytosine complexes.…”

Diagnostic optical sequencing

“…Due to the distinct biochemical nature of the nucleobases in DNA, each has unique interactions with light photons and a unique Raman spectrum. [31][32][33][34] With SERS measurements, surface plasmon polaritons squeeze light photons with several hundred-nanometer wavelengths into molecular length scales, where they can interact with the nucleotides in DNA. 25,35,36 Despite the advances in nano-optics and three-dimensional plasmonic nanofocusing, the nanometer scale mode volumes prevent characterization of photon interactions with single nucleotides.…”

“…For BOS, we identified a single distinctive Raman peak for each nucleobase as the "signature peak" which is later used to determine content in unknown sequence blocks. For purines, we selected the ring breathing modes at ~740 cm -1 for A and ~690 cm -1 for G. 29,31,34,40,42 For pyrimidines, we selected the ring bending modes at ~600 cm -1 for C and ~460 cm -1 for T. 29,32,33,40,42 Within each SERS measurement, the PO2stretching mode peak at 1089 cm -1 due to the phosphate backbone is used as an internal standard for normalizing the relative peak intensities, as is consistent with other studies employing nanoparticle substrates. 27,40 All signature peaks and the PO2normalization peak are highlighted in Figure 1b.…”

Recent advances in linear and nonlinear Raman spectroscopy. Part IV

“…Their results were used to deduce the formation of an RNA hairpin whose secondary structure is consistent with that proposed on the basis of phylogenetic comparisons with other viral RNAs. Shanmugasundaram and Puranik [75] review the performance of DFT methods in the prediction of nucleobases and their analogs and find that even with modest basis sets, trends in vibrational spectra can be predicted adequately and guide assignments to the normal modes of the molecule. The vibrational properties of both wild-type and selenomethionine (SeMet)-substituted protein SOUL crystals were investigated by Rossi et al [76] using Raman spectroscopy.…”