The helix to coil transition, or DNA melting, is one of the fundamental processes of life. Nevertheless, it is difficult to achieve an atomistic description of this reaction in solution with current spectroscopic techniques. On the other hand, the computer simulation of DNA melting poses a formidable challenge for theoretical chemists as, even for short sequences, the process occurs in nature on the millisecond or longer time scale. For this reason, this type of simulation has not been attempted yet and the accuracy of force fields in reproducing the free energy of DNA hybridization is not known. Here it is shown how, by combining replica exchange and metadynamics, it is possible to simulate the helix to coil transition of DNA hexamers at room temperature and characterize the reaction intermediates and the relative free energy of hybridization. Three sequences were investigated with both the standard Amber99 force field and a version with modified phosphate torsion parameters [Peres, A.; et al. Biophys. J. 2007, 92, 3817-3829]. It is shown that the Amber99 force field overestimates the stability of single stranded and noncanonical DNA that are predicted to be thermodynamically more stable than canonical B-DNA. Therefore this force field is not suitable for DNA studies where large conformational changes occur. The changes introduced by Peres et al. significantly improve the agreement with the experiment. However, the stability of one of the sequences investigated is still underestimated by the modified force field. It is concludes that, although current force fields can provide a reasonable picture of the hybridization reaction, a polarizable force field may be required to obtain a more quantitative agreement with the experimental free energies of hybridization.