Atomistic molecular dynamics simulation of a 94-bp DNA minicircle

Properties of DNA fragments around 100 bp in length are of prominent biological interest - loops of similar sizes are involved in gene regulation and, complexed with the histone core, they form nucleosomes, the basic structural units of DNA spatial organization in eukaryotic cells. Recent experiments have revealed that DNA fragments of such size form closed loops (circles) with much lower energetic cost than predicted by standard theories of DNA elasticity. This finding has inspired a rich theoretical work aimed at explainig the discrepancy. The proposed models assume a localized structural transition in DNA (bubble, or kink) but differ as to how this alternate structure looks like. To shed more light onto the problem, we performed a series of atomic resolution molecular dynamics simulations of a 94-bp DNA minicircle with explicitly represented water and ions. The results of the simulations, which expose both advantages and limitations of the chosen method, will be presented, and the relationship to theory and experiments on DNA cyclization will be discussed.

Course work

This talk also serves as an introduction to a course on simulations of DNA/RNA held in the computer lab (017) of the mathematical department  (FU Berlin) during the same week.

References

• A Perez, A Noy, F Lankas, F Javier Luque and M Orozco
  The relative flexibility of B-DNA and A-RNA duplexes: database analysis
  Nucleic Acids Res. 32, 6144-6151 (2004)
   

• A. Noy, A. Perez, F. Lankas, F. Javier Luque and M. Orozco
  Relative Flexibility of DNA and RNA: a Molecular Dynamics Study
  J. Mol. Biol. 343, 627-638 (2004)
   

• D. L. Beveridge, G. Barreiro, K. S. Byun, D. A. Case, T. E. Cheatham III, S. B. Dixit, E. Giudice, F. Lankas, R. Lavery, J. H. Maddocks, R. Osman, E. Seibert, H. Sklenar, G. Stoll, K. M. Thayer, P. Varnai and M. A. Young
  Molecular Dynamics Simulations of the 136 Unique Tetranucleotide Sequences of DNA Oligonuleotides. I.Research Design and Results on d(CpG) Steps
  Biophys. J. 87, 3799-3813 (2004)
   

• F. Lankas, J. Sponer, J. Langowski,  T. E. Cheatham,III
  DNA Deformability at the Base Pair Level
  J. Am. Chem. Soc. 126, 4124-4125 (2004)