Biophysicist studies electrostatics, which may hold the key to the body's cell interactions

Published: July 14, 2011

Tom Hallman
Media Relations

Meandering about your body right now are billions of molecules, all going about their business and interacting with one another to make you — your biological system — work right.

Every now and then, one of those little interactions goes awry. The resulting confusion can lead to big problems, including severe disease.

To get to the bottom of it all, scientists first need to understand more about the way these molecules interact. One such way — a kind of molecular handshake — is electrostatic force.

"Electrostatics is the major force between molecules," said Clemson University biophysicist Emil Alexov, one of the scientists studying these interactions. "Understanding that, you understand how they function in the cell and how disease affects their functionality."

Being collections of charged particles, molecules naturally carry tiny electrical charges. Scientists have been testing the effects of these charges ever since physicist J. J. Thomson discovered the electron in his work on cathode rays in 1897, so plenty already is known about electrostatics.

Applying those rules to the molecules in your body is more dicey, mainly because there are so many charged particles at work, and they're all moving targets.

"The living cell is a very complicated system comprised of biological macromolecules such as DNA, RNA and proteins. They constantly interact with each other to maintain the function of the cell and the main driving force is the electrostatics," said Alexov, who is an associate professor of physics.

"Each of these atoms has a charge, and they are all in water — not a homogeneous medium — so you're working with millions of atoms whose positions are not defined," he said. "Because of that, accurate calculations of electrostatic fields and energies are crucial for successful modeling of virtually all biological processes and many other phenomena occurring in nanosystems and nanodevices."

To determine how all these charged particles will behave requires some complicated math. Based on nearly century-old mathematical theory, the Poisson-Boltzmann equation, a differential equation that describes electrostatic interactions, serves as the basis for Alexov's work. It allows scientists to calculate the corresponding energies for molecules and geometrical objects immersed in water or other solutions.

But to make that equation function on the scale necessary to study living organisms, where the stakes are high and the variables nearly infinite, you need a really big computer and some top-flight software.

In Alexov's case, the computer is right on campus: Clemson's Palmetto Cluster is ranked among the top 100 supercomputers in the world. Alexov's research team is one of its largest users.

The software for his project, called DelPhi, was developed specifically to handle the math of the Poisson–Boltzmann equation. Alexov served for five years as senior researcher in the lab of its creator, Barry Honig of Columbia University. At Clemson, part of his work is to improve the software's speed and accuracy, continuously adapting the program so that scientists across the world can apply it to the rapidly changing areas of computational biophysics and bioinformatics.

It's all highly specialized, but in this field of research it's the only way to get the job done, he said.

"You couldn't achieve this with laboratory experiments," Alexov said. "If you had to do this experimentally in a lab, it would cost you a billion dollars. Modeling is much faster, much cheaper."

It has other benefits as well.

"With proper mathematical modeling, study can be done on a large number of cases so it will have more validity," Alexov said. "In an experiment, the results are specific to the object you are studying, but we can apply this model to numerous cases to provide more reliable data."

An indication of the importance that scientists put on his work is the support Alexov has garnered. His research is sponsored by five-year, $2.2 million grant from the National Institute of General Medical Sciences, a part of the National Institutes of Health. The project is an international collaboration with the Italian Institute of Technology.

Ultimately Alexov's team, which includes several graduate and undergraduate students at Clemson, will develop new capability in the DelPhi software to allow scientists to study areas previously inaccessible to them.

At the same time, they work directly with scientists engaged in laboratory experiments so they can better understand the molecular mechanisms of biological systems.

Portions of Alexov's work are devoted to estimating pKa values of amino acids, which play an important role in defining the characteristics of proteins, and probing disease-causing missense mutations, which can keep proteins from functioning.

"Modeling is a very efficient and fast approach to deliver important biological information," Alexov said. "Currently, we can calculate the electrostatic potential and the corresponding energies and carry detailed analysis of the structure-function relationships in a relatively short time period. As this ability develops, it will help us shorten the time for developing new treatments for human diseases."

Emil Alexov (864-656-5307) is an associate professor in the biophysics group in the physics and astronomy department at Clemson University.