NCSA is arming a team of young scientists with the supercomputing resources necessary to engage in the battle against cancer. This team of undergraduate physical, biological, and computational chemists at New York's Hamilton College joins the front line in computational research on enediynes, naturally occurring molecules commonly called biological warheads for their ability to bind to and split tumors' DNA backbones. Using NCSA's SGI Origin2000 supercomputer, the students are contributing knowledge of new cancer treatments and using computational chemistry in an authentic team research setting.

Esperamicin binds to DNA just before Bergman cyclization. Enlarge image.

Scientists became interested in the antitumor activity of enediyne antibiotics such as dynemicin, calicheamicin, and esperamicin because of the molecules' low thermal barriers to Bergman cyclization. Bergman cyclization is a reaction in which the enediyne converts to an intermediary benzene diradical, an aromatic ring missing two carbon-hydrogen bonds. When the molecule is in the intermediary diradical state, it can forcibly extract hydrogen from deoxyribose carbons to split DNA, resulting in the death of the cancerous cell.

The temperature barrier is the amount of energy that must be applied to the molecule to cause a reaction. This level is particularly important to drugs' effectiveness because it determines whether Bergman cyclization will occur at human body temperature. Many scientists are trying to synthesize or computationally design molecules that only cyclize when they've taken on an additional hydrogen ion, a process that occurs readily in acidic solutions. The challenge is to find or create an enediyne-containing molecule that is completely unreactive under the normal pH of a healthy cell, yet takes on an additional hydrogen ion in acidic cancerous cells and becomes reactive.

Access Online | Posted 1-15-2002