Supercomputer paints electric landscape

Researchers at the University of California, San Diego have mapped key cellular structures using a new method to harness the power of supercomputing.

CA-Researchers at the University of California, San Diego have mapped key cellular structures using a new method to harness the power of supercomputing.

The maps may point the way to understanding how those structures perform functions such as transporting a drug like taxol to a binding site where it can do its work in treating breast cancer.

‘We’ve achieved a new landmark in the scale of cellular structures that we can model from a molecular perspective,’ said J. Andrew McCammon, Joseph E. Mayer Professor of Theoretical Chemistry at UCSD and a Howard Hughes Medical Institute investigator. ‘The work signals a new era of calculations on cellular-scale structures in biology.’

The researchers created a new method for solving what is known as known as thePoisson-Boltzmann equation.

This allowed them to increase the size of the systems they could model from less than 50,000 atoms to over a million atoms.

The maps are said to depict an atom-by-atom rendering of the electrostatic potential of structures found within cells: microtubules, which are 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, for example, the electric forces that draw a taxol molecule through a microtubule and into a binding site or that pull a tRNA molecule into place on a ribosome during translation.

To model the structures, McCammon and his colleagues created algorithms and wrote computer codes to solve equations that describe the electrostatic contributions of individual atoms within a system. Previous work had been limited by the numbers of atoms that could be modelled at once and how the computers could utilise the code.

The system could be enlarged even further, 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 small portion of the calculation to each available processor on the computer.

Those processors then independently solve their portion of the equation and pass the results along to a ‘master processor’ that gathers and processes the data.

Blue Horizon, a large IBM SP, 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 discovered some small islands of positive potential in the overall negatively charged microtubule.

They said that while the negative charge likely plays a strong role in intracellular transport, the overall topography points to regions where drugs like taxol and colchicine may bind.

Likewise, the electrostatic map of the ribosome revealed an area on the smaller 30s subunit that may play roles in stabilising tRNA and mRNA during translation.