NCSA NEWS

Slight structural variations within a stretch of DNA cause it to bend in ways that determine whether a gene sits dormant or cranks out thousands of copies. Scientists are uncovering how molecular dynamics govern this bending.

Blue eyes or brown, tall or short, susceptible to cancer or diabetes--our characteristics are written in the code of a twisting double helix. Unraveling that code has occupied molecular biologists since 1953, when James Watson and Francis Crick first proposed the double helical structure of DNA. This long molecule resembles a twisting rope ladder, the legs of which are identical groups of sugars and phosphates. The rungs, however, are composed of four kinds of bases. In genes, regions that code for proteins, the bases exist in any of 64 different groupings of three. These groupings, called codons, form the words of the genetic language--a language that carries the instructions for building and maintaining a living organism.

Over the years scientists have learned that a source of nuance in the meaning of this genetic language lies in structural variations that arise from differences in the sequence not of codons but of the bases themselves. Differences in base sequence encourage certain stretches of the double helix to fold back upon itself as if making a U-turn, while other stretches are straight as rods. Some stretches twist tightly, like an overwound rubber band, whereas others curve gently. These twists and bends often influence whether a gene sits dormant or turns on to crank out thousands of copies of a protein.

Today genetic engineers can design DNA with any base sequence, but they still cannot predict how it will twist or bend. To improve predictability, molecular biophysicist David Beveridge and his colleagues at Wesleyan University in Middletown, CN, are modeling DNA on the SGI Cray Origin2000 computer at NCSA. Graduate student Matthew Young generated the first glimpse of the bending action of a well-studied stretch of DNA called phased A-tract. The results, reported in the Journal of Molecular Biology, may lead to a fundamental understanding of the molecular forces that bend DNA.

Access Online | Posted 5-18-1999