NUMERICAL SIMULATION OF THE IR SPECTRA OF DNA BASES

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1 BIOPHYSICS NUMERICAL SIMULATION OF THE IR SPECTRA OF DNA BASES C. I. MORARI, CRISTINA MUNTEAN National Institute of Research and Development for Isotopic and Molecular Technologies P.O. Box 700, R Cluj-Napoca 5, Romania Received December 21, 2004 Our present study reports the IR spectra of each separate DNA base: adenine (A), cytosine (C), thymine (T) and guanine (G). The simulations were performed at ab initio level using the DZ gaussian basis set. The steps of the simulations were the following: (i) optimisation of the geometry for each DNA base; (ii) computing the hessian matrix and the IR spectra for each DNA base by using the ab initio dipolar moments. All the calculations were performed using the GAMESS package. Each simulation is reported separately for A, C, T and G. As a first approach for the IR spectrum of the whole DNA molecule we use the overlap of these four spectra. Key words: DNA bases, ab initio, IR spectra. 1. INTRODUCTION DNA is a very important biological molecule since it carries the genetic code. The famous double helix structure has emphasized the relationship between structure and function. In the specific case of DNA, understanding the processes by which specific binding sites are recognized by drugs, mutagens, proteins and other molecules would represent a fundamental step towards understanding its biological activity. Vibrational spectroscopy was presented as an alternative structural approach for the study of nucleic acids and their complexes, particularly for investigating the aqueous solution structures and the interactions of large oligonucleotides, native nucleic acids and their biological assemblies, like chromosomes and viruses. The high information content of vibrational spectra is reflected in the many new insights that have been obtained into the conformation, composition, interaction and functioning of DNA molecules. As a first approach of comparing the experimental results of DNA molecule with theoretical calculations, our present study reports the IR spectra of each separate DNA base (adenine, cytosine, thymine and guanine) and the overlap of these four spectra. Paper presented at the 5th International Balkan Workshop on Applied Physics, 5 7 July 2004, Constanþa, Romania. Rom. Journ. Phys., Vol. 50, Nos. 9 10, P , Bucharest, 2005

2 1152 C. I. Morari, Cristina Muntean 2 2. COMPUTATIONAL METHODS In order to compute the normal modes of a polyatomic molecule, we have to build the Hessian matrix F ij [1]. The eigenvalues for the vibrational modes are the results of the following system ( ij ij F δ λ k) ljk = 0 (1) j which can be solved by asking to its determinant to vanish. det( Fij δijλ ) = 0. (2) The final vibrational frequencies are k ν k =λk 1/2 /2π (3) where λ k are the frequencies resulting from the Eq. (1). All the calculation presented below are performed using the GAMESS implementation of this scheme [2]. Fig. 1. The structures of cytosine (C) and guanine (G). Fig. 2. The structures of adenine (A) and thymine (T).

3 3 IR spectra of DNA bases 1153 The structure for all DNA components were optimized using the DZ basis set [3]. The resulting geometries are depicted in Figs. 1 and RESULTS The vibrational analysis was performed by computing the Hessian matrix and the force constants for all normal modes of each DNA base. The computed frequencies were scaled with a factor of 0.89 in order to remove the effect of the harmonic oscillator approach upon the computed frequencies [4]. The resulting IR spectra are given in Figs. 3 and 4. Fig. 5 is the overlap for all 4 spectra computed independently. Fig. 3. The IR spectra of cytosine (left) and guanine (right). Fig. 4. The IR spectra of adenine (left) and thymine (right). The most intense contributions to all IR spectra is located near 1600 cm 1. In this region bands were assigned experimentally to N-H and C-O vibrations. A list with the most intense IR bands resulting from our simulation is given below. As can be seen from the Table 1, the most intense IR bands are those involving out-of-plane hydrogen torsional motion. The relatively large values of

4 1154 C. I. Morari, Cristina Muntean 4 Fig. 5. Overlap of the spectra given in the Figs. 3 and 4. Table 1 The most intense IR bands in the simulated spectra for each DNA base together with their assignments. The numbering scheme is given in Figs. 1 and 2. DNA base Frequency [cm 1 ] Assignment C 809 tors: ; tors: ; bend:2-1-9 G 553 tors: ; tors: ; tors: T 654 tors: ; tors: A 833 bend:4-3-10; tors: the dipolar moment of such oscillations suggest that the electric charge has the tendency to remain confined to the C-C bonds while the hydrogen motion does not involve a corresponding motion of the electronic charge that populates the molecular orbitals of the base pairs. CONCLUSION An ab initio simulation of the IR spectra for the DNA bases was performed. The results confirm the previously experimental assignments. Significant difference of the IR intensity for the simulated and experimental spectra exist. This is a clear indication of the influence of the interactions between base pairs and of the solvent effects upon the computed IR intensities. The most intense bands were assigned to the out of plane hydrogen torsional motions.

5 5 IR spectra of DNA bases 1155 REFERENCES 1. I. N. Levine, Quantum Chemistry, Prentice Hall, (2000). 2. M. W. Schmidt, K. K. Baldridge, J. A. Boatz, S. T. Elbert, M. S. Gordon, J. H. Jensen, S. Koseki, N. Matsunaga, K. A. Nguyen, S. J. Su, T. L. Windus, M. Dupuis, J. A. Montgomery, J. Comput. Chem., 14, 1347 (1993). 3. T. H. Dunning Jr., P. J. Hay in Methods of Electronic Structure Theory, H. F. Shaefer III, Ed. Plenum Press, N.Y. (1977). 4. A. P. Scott, L. Radom, J. Phys. Chem., 100, (1996). 5. C. M. Muntean, Teza de doctorat, Cluj-Napoca, (2002).