To replicate a single unit of human DNA, about 3 billion individual base pairs are joined. In the course of building a baby from a fertilized egg, this process goes on about a million billion times. Despite the seemingly infinite room for error, however, a mistake is made only once for every 10 billion operations.
That means there's an impressive quality control system at work. One part of this DNA copying machine is the polymerase, protein enzymes that make sure complementary bases are placed with one another as a strand of bases becomes duplicated DNA. Mechanisms that repair and ensure the fidelity of DNA during its replication are vital since many human diseases can originate from mutations that are the result of polymerase error.
An interdisciplinary team of investigators from New York University (NYU) and the National Institute of Environmental Health Sciences (NIEHS) are using the Alliance's SGI Origin2000 supercomputer at NCSA to create the first molecular dynamics simulations to show the sequence of actions of a particular polymerase known as pol as it takes part in the DNA repair process.
The team includes Tamar Schlick, a mathematics, chemistry, and computer science professor at NYU; Suse Broyde, a biology professor at NYU; Samuel H. Wilson, deputy director of NIEHS; Linjing Yang, Schlick's postdoctoral associate; and Bill Beard, Wilson's colleague at NIEHS.
Broyde, who is interested in polymerase mechanisms in relation to mutagenesis and carcinogenesis by environmental carcinogens via computer simulations, and Wilson, who is a leading experimentalist investigating pol , collaborated previously in the molecular dynamics simulation of carcinogen-damaged DNA within pol . Schlick, meanwhile, pioneered the development of new algorithms for dynamic simulations that provide significant speedup. On a visit to NYU, Wilson proposed to Broyde investigating the opening-closing motion of pol thought to be crucial to the polymerase's DNA repair function. Broyde immediately suggested recruiting Schlick, whose algorithms proved key to sampling and zooming in on some of the large-scale enzyme motions of pol that are biologically relevant.
"Biologists are realizing the growing insights that can emerge from theoretical studies, including molecular dynamics simulations," says Schlick, who also uses NCSA's Origin2000 to research the eukaryotic transcription TATA-box binding protein and DNA complex in collaboration with crystallographer Steven Burley at Rockefeller University. "Strong collaborations between experimentalists and theoreticians will be key in future structure biology research."
Access Online | Posted 3-13-2001