Computational determination of radiation damage effects on DNA structure

• Authors: Miroslav Pinak
• Languages of publication: EN

Abstracts

EN

Molecular dynamics (MD) studies of several radiation originated lesions on the DNA molecules are presented. The pyrimidine lesions (cytosinyl radical, thymine dimer, thymine glycol) and purine lesion (8-oxoguanine) were subjected to the MD simulations for several hundred picoseconds using MD simulation code AMBER 5.0 (4.0). The simulations were performed for fully dissolved solute molecules in water. Significant structural changes in the DNA double helical structure were observed in all cases which may be categorized as: a) the breaking of hydrogen bonds network between complementary bases and resulted opening of the double helix (cytosinyl, radical, 8-oxoguanine); b) the sharp bending of the DNA helix centered at the lesion site (thymine dimer, thymine glycol); and c) the flippingout of adenine on the strand complementary to the lesion (8-oxoguanine). These changes related to the overall collapsing of the double helical structure around the lesion, are expected to facilitate the docking of the repair enzyme into the DNA in the formation of DNA-enzyme complex. The stable DNA-enzyme complex is a necessary condition for the onset of the enzymatic repair process. In addition to structural changes, specific values of electrostatic interaction energy were determined at several lesion sites (thymine dimer, thymine glycol and 8-oxoguanine). This lesion-specific electrostatic energy is a factor that enables repair enzyme to discriminate lesion from the native site during the scanning of the DNA surface.

Keywords

EN

molecular dynamics; DNA lesions; repair enzymes; 31.15.Qg

• Publisher: De Gruyter Open
• Journal: Open Physics
• Year: 2003
• Volume: 1
• Issue: 1
• Pages: 179-190

Dates

published

1 - 3 - 2003

online

1 - 3 - 2003

Contributors

author

Miroslav Pinak

• Japan Atomic Energy Research Institute, Shirakata Shirane 2-4, 319-1195, Tokai-mura, Ibaraki-ken, JAPAN

References

• [1] Harrison, S. and Aggarwal, A., Annu. Rev. Biochem. 59 (1990) 933. http://dx.doi.org/10.1146/annurev.bi.59.070190.004441[Crossref]
• [2] Gicquel-Sanzey, B. and Cossart, P., EMBO J. 1 (1982) 591.
• [3] Ham, J., Thompson, A., Nedham, M., Webb, P. and Parker, M., Nucleic Acid Res. 16:12 (1988) 5263.
• [4] Beato, M., Cell 56 (1989) 335 http://dx.doi.org/10.1016/0092-8674(89)90237-7[Crossref]
• [5] Harris, L., Sullivan, M. and Hickok, D., Computers and Mathematics with Applications 20 (1990) 25. http://dx.doi.org/10.1016/0898-1221(90)90312-8[Crossref]
• [6] Marx, J., Science 229 (1985) 846. http://dx.doi.org/10.1126/science.2992087[Crossref]
• [7] Matthews, B., Nature 335 (1988) 294. http://dx.doi.org/10.1038/335294a0[Crossref]
• [8] Harris, L., Sulliwan, M. and Hickok, D., Proc. Natl. Acad. Sci. USA 90 (1993) 5534. http://dx.doi.org/10.1073/pnas.90.12.5534[Crossref]
• [9] Case, D.A., Pearlman, D.A., Caldwell, J.W., Cheathman III, T.E., Ross, W.S., Simmerling, C.L., Darden, T.A., Merz, K.M., Stanton, R.V., Cheng, A.L., Vincent, J.J., Crowley, M., Ferguson, D.M., Radmer, R.J., Seibel, G.L., Weiner, P.K. and Kollman, P.A., AMBER 5.0, (1997) University of California San Francisco.
• [10] Smith, P.E. and Petit, B.M., J. Chem. Phys., 105 (1996) 4289. http://dx.doi.org/10.1063/1.472246[Crossref]
• [11] Pinak, M., Yamaguchi, H. and Osman, R., J. Radiat. Res. 37 (1996) 20. http://dx.doi.org/10.1269/jrr.37.20[Crossref]
• [12] Pinak, M., J. Mol. Struct.: THEOCHEM 466 (1999) 219. http://dx.doi.org/10.1016/S0166-1280(98)00513-2[Crossref]
• [13] Pinak, M., J. Mol. Struct.: THEOCHEM 499 (2000) 57. http://dx.doi.org/10.1016/S0166-1280(99)00277-8[Crossref]
• [14] Pinak, M., JAERI-research 2001-038, (2001).
• [15] Pinak, M., J. Comput. Chem. Vol. 22, Iss.15 (2001) 1723. http://dx.doi.org/10.1002/jcc.1127[Crossref]
• [16] Pinak, M.J. Mol. Struct.: THEOCHEM 583/1-3 (2002) 189.

Identifiers

DOI

10.2478/BF02475560