Since we were developing DNA diagnostic technology that involved extending and stretching DNA, we wondered how much tension could be supported by a small helix before the strands were pulled apart or broken. In fact, in 1994, a group at the Naval Research Labs in Washington DC used the atomic force microscope to measure the force required to separate one DNA helix 12 base pairs long [Lee et al., Science 266: 771, 1994]. It was a relief to find that their value was about 1000 fold greater than the forces exerted on the beads by the electric fields used in our diagnostic.

We believed computer simulations using molecular dynamics would enable us to explore a variety of questions about the response of DNA to tension and started with the same double stranded 12-mer used by the Lee et al. We were pleased to see the strands separate in our simulation at the same tension as seen by Lee's group. However, before strand separation, as increasing tension caused the DNA to stretch to about twice it's length, we were surprised to see a sudden increase in length and a transition to a flat ribbon structure. Reading the literature (always a good idea) revealed that in the previous year, Bensimon et al. [Physical Rev Lett, 74:4754, 1995] showed that DNA could be stretched on the surface of a liquid to about two times its original length before breaking. Then, two groups, in back to back papers [Cluzel et al., Science 271:792 and Smith et al., ibid 271:795, 1996] determined quantitative extension versus tension curves for DNA, and found a sharp 2X length extension at the same value seen in our simulations. We published our results a few months later in the November 13 th issue of the Journal of the American Chemical Society.

Double stranded DNA is not the only molecular complex that is greatly elongated as one part is pulled from the other. The computer simulation by Grubmuller et al. [Science 271:997, 1996] of the separation of the biotin-streptavidin complex, shows a high tension over a distance of at least 0.9 nm (9 A) on biotin as it is removed from the binding pocket. As with DNA, this long dissociation path is possible because the complex deforms as the biotin is removed.

However, the formation of a molecular complex usually takes place over a smaller distance, and is not associated with large, energy requiring deformations of it's two parts. Thus, association and disassociation, in these cases, occurs by different pathways. In order to predict the stability of such a complex, it is necessary to know details of association and dissociation, knowledge of the energy of the complex alone is not sufficient. In order to model dissociation processes, it desirable to have powerful molecular dynamics software, which we are developing,