It has been speculated that bubble formation of several base-pairs due to thermal fluctuations is indicatory for biological active sites. Recent evidence, based on experiments and molecular dynamics (MD) simulations using the Peyrard-Bishop-Dauxois model [1,2], seems to point in this direction [3,4]. However, sufficiently large bubbles appear only seldom which makes an accurate calculation difficult even for minimal models. In this talk, I introduce a new method that is orders of magnitude faster than MD.  Using this method we are able to show that the present evidence is unsubstantiated [5].

[1] M. Peyrard and A. R. Bishop, Phys. Rev. Lett. 62,  2755  (1989).

[2] T. Dauxois, M. Peyrard, and A. R. Bishop, Phys. Rev. E 47,  684  (1993).

[3] C. H. Choi , G. Kalosakas, K. O. Rasmussen, M. Hiromura, A. R. Bishop, A. Usheva, Nucl. Acid Res. 32, 1584  (2004).

[4] G. Kalosakas, K. O. Rasmussen, A. R. Bishop, C. H. Choi, A. Usheva, Eur. Phys. Lett. 68, 127 (2004).

[5] T. S. van Erp, S. Cuesta-Lopez, J.-G. Hagmann, and M. Peyrard, accepted for publication in Phys. Rev. Lett.