A new method for studying the electrical charges of large biological molecules may enable researchers to make a leap from modeling molecules of 50,000 atoms to those of more than a million atoms. This may make it possible to develop more effective anti-cancer drugs.

View a QuickTime movie of a “fly-through” of a microtubule
The technique, developed by Howard Hughes Medical Institute (HHMI) researchers at the University of California, San Diego (UCSD), was used to model the electrostatic properties of microtubules and ribosomes.

Electrostatic models portray how the charges on individual atoms of a molecule interact to produce a distribution of electric fields throughout the molecule. The models can help researchers analyze the stability and dynamic motions and interactions of biological molecules.

The “parallel focusing” method enables solution of the Poisson-Boltzmann equation (a fundamental equation in the field of electrostatics) to be run efficiently and flexibly on parallel computers.

Applying this method to a model of a 1.25-million-atom microtubule revealed large-scale “undulations” in electrical potential. The scientists also found that the electrostatic potential at each end of the microtubule was different, which may provide clues to the stability of microtubules.

“Understanding microtubule instability and the mechanism by which microtubules dissociate could have therapeutic applications because many anti-cancer drugs act to stabilize microtubules,” said HHMI lead investigator J. Andrew McCammon.