DNA Oligonucleotide−cis-Platin Binding:  Ab Initio Interpretation of the Vibrational Spectra

Abstract

The cis-platin binding to the d(CCTGGTCC)*d(GGACCAGG) model DNA octamer was monitored with infrared absorption (IR) and vibrational circular dichroism (VCD) spectroscopies. The spectra were modeled with the aid of density functional computations and a Cartesian coordinate-based transfer of molecular property tensors from smaller DNA fragments. Because of the fragmentation, the tensors could be calculated with a higher precision. Environmental effects, such as the presence of the solvent or the cis-platin ligand, could be included in the modeling. The solvent was modeled by an explicit inclusion of hydrogen-bound water molecules, positions of which were estimated from a molecular dynamics simulation, or by the polarized continuum COSMO model. The B3LYP and BPW91 functionals used for the calculations of the spectral parameters were combined with the relativistic LANL2DZ platinum pseudo-potentials. The simulations reproduced the main IR and VCD DNA spectral features and explained most of the changes observed experimentally upon metal binding. The results confirmed that the influence of the ligand on DNA vibrational properties is quite complex; it originates in the geometry deformation and normal mode coupling pattern changes of the platinated octamer, as well as in local perturbations of the electronic structure and force field of the GC base pairs to which the platinum is bound. Many of the local effects could be accounted for by a point charge used in place of the metal in the GC complex.

Infrared Absorption Detection of Metal Ion-Deoxyguanosine Monophosphate Binding: Experimental and Theoretical Study

“…As pointed out previously 29 and also confirmed by the frequency shifts listed in the present study in Table 3, many of the dGMP vibrational changes caused by the metal ions can be induced purely electrostatically by point charges. For example, the CdO stretching frequency (1678 cm -1 ) increased to 1688 cm -1 by the copper ion undergoes a similar shift to 1684 cm -1 if the +2e charge is placed at the same position.…”

“…[28][29][30][31] In the past, such computations provided preferential geometries and binding sites and could explain different DNA affinity to different metals. [32][33][34] Because of the computational limits, the modeling is often restricted to simplified nucleic acid components.…”

Molecular dynamics with restrictions derived from optical spectra

“…(8)] displayed at the bottom of Figure 8 appear even more practical: the preferential conformation can be recognized already at a shorter time (0.1 ns) and, similarly as for the one-dimensional H 2 O 2 problem, the distribution is much sharper than that obtained by SRMD (upper part of Fig. 8).…”

“…The two-dimensional projections of the 3D probability distributions obtained by the second method [eq. (8)] are shown in Figure 10. The distributions are relatively sharp, narrower than those obtained from the unconstrained MD run (bottom part of Fig.…”

“…The vibrational circular dichroism (VCD) 5 and the Raman optical activity (ROA) 6 gave unique information about structure of many organic compounds, proteins, or nucleic acids. 7,8 Other important ways to increase effective resolution of the optical spectra include site-specific labeling with stable isotopes 9 and twodimensional multiphoton spectra sampling the chromophore coupling. 10 Simulations by modern quantum-chemical methods represent powerful tools for the spectra interpretations.…”