By Richard Acello
Small Times Correspondent
Sept. 10, 2001 — Researchers at the University of California, San Diego (UCSD) are using supercomputing power to form maps of cellular structures.
The maps may help scientists discover how cell structures transport a drug such as taxol to a binding site so it can do its work in treating breast cancer.
“The work signals a new era of calculations on cellular-scale structures in biology,” according to J. Andrew
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| Simulated images of the barrel-shaped microtubule exterior and interior, seen as both side and end-on views. The purple areas dotted throughout the red subunits comprising the microtubule represent areas that play a key role in transporting drugs such as taxol to their binding sites. |
Development of better computer modeling is considered by scientists to be an important next step in the progress of nanotechnology. There is a need to better understand how structures behave on the nanoscale.
The UCSD researchers created a new method for solving what is known as the Poisson-Boltzmann equation. This allowed them to increase the size of the systems they could model from fewer than 50,000 atoms to more than an unprecedented one million atoms. McCammon likened the ability to pick out one atom within such a large three-dimensional system as being able to specifically describe one cherry within an entire fruit tree.
The maps depict an atom-by-atom rendering of the electrostatic potential of structures found within cells including microtubules, involved in intracellular transport and shape, and ribosomes, which manufacture proteins. Electrostatics describe the way in which the landscape of electrical charge is laid out in a molecular environment, such as the electric forces that draw a taxol molecule through a microtubule and into a “binding site” that tugs a molecule into place on a ribosome.
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McCammon said that based on his experience in developing molecular computer simulations of proteins and nucleic acids and the methods for using them to calculate the strength of binding of pairs of molecules, there will be “strong interest within two to five years from drug companies. “That’s the time it seems to take for practical applications to emerge and stimulate a commercial response,” McCammon said.
Nanoscale maps could also be used in the materials arena, McCammon said. Many molecular assemblies, chips, and other devices are governed in their assembly and behavior by electrostatic interactions, he added.
The calculations were performed at the San Diego Supercomputer Center (SDSC) at UCSD on Blue Horizon, an IBM supercomputer supported by the National Partnership for Advanced Computational Infrastructure (NPACI). The study appears online and in print in the Proceedings of the National Academy of Sciences.
To model the structures, McCammon and his research group created algorithms and wrote computer codes to solve equations that describe the electrostatic contributions of individual atoms.
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The research could be extended, said Nathan Baker, a postdoctoral researcher in McCammon’s lab. “The calculations were done in a highly scalable fashion and would be suited to even larger runs. We hope to push the envelope even further and to tackle a number of large-scale problems in intracellular activity such as antibiotic binding to ribosomes,” he said.
The new algorithm assigns a portion of the calculation to available processors on the computer. The processors solve their portion of the equation and pass the results along to a “master processor” that gathers the data. Blue Horizon completed the calculations for the equation relating to the microtubule in less than an hour using 686 processors available out of 1,152. The researchers estimated that the old method would have required at least 350 times more memory and time to solve.
As a result of their calculations on the microtubule, the researchers said the topography of the cellular structures points to regions where drugs like taxol may bind.
Baker was supported by a predoctoral fellowship from the Howard Hughes Medical Institute and the Burroughs-Wellcome La Jolla Interfaces in Science program. The research is also supported by IBM, the National Institutes of Health, National Science Foundation, NPACI/SDSC, and the W.M. Keck Foundation.
SDSC is a research unit of the University of California San Diego, and is sponsored by the National Science Foundation through NPACI and by other federal agencies, the State and the University of California, and private organizations.