Maria Kurnikova
Assistant Professor of Chemistry
Maria Kurnikova (second from left) and her research group.
Research Interests
Kurnikova specializes in developing computational models of the dynamics of proteins and protein assemblies on a long time scale. She is particularly interested in analyzing ion channels, including the relationship between structure and function, to understand how molecules move the channels and how the channels open and close. In-depth studies of ion channels, which are critical to life, will aid the development of drugs for a variety of diseases and the design of nanoscale biosensors for medical applications.
Professional Background
Ph.D. Physical Chemistry, University of Pittsburgh, 1998
M.S. Physical and Chemical Biology, Moscow Institute of Physics and Technology, 1990
After receiving her doctorate from the University of Pittsburgh, Kurnikova was a postdoctoral fellow at the University of Tel Aviv, Israel. She returned to the University of Pittsburgh as a research associate in 1999. During that time she also held an appointment as a guest researcher at the National Institute of Standards and Technology. She was an assistant professor of physical chemistry at Marquette University until she joined Carnegie Mellon’s faculty in 2003. Last year Kurnikova gave invited talks at the Quantum Theory Project’s Sanibel Symposium, the Gordon Conference on Computational Chemistry and a Federation of American Societies for Experimental Biology Summer Research conference on the biophysics of cell membranes.
What are ion channels and why it is important to study them?
Ion channels are proteins that act as a sort of tunnel through the cell membrane, transporting ions — electrically charged atoms or molecules — into and out of the cell. There are different channels for different ions, and each carries out a specific function. For instance, chlorine channels in stomach cells maintain acidity and sodium channels in nerve cells regulate electrical signals. Defects in ion channels, or in the molecules that interact with them, can lead to a number of disorders, including cystic fibrosis, epilepsy, and migraine headaches. The better we understand how ion channels work, the better we can design drugs that act only on specific ion channels.
What methods are you using to study ion channels?
A typical way to determine a protein’s 3D structure is to isolate it and crystallize it. Proteins that span the cell membrane, such as ion channels, are difficult to crystallize, which makes determining their structure very complicated. Even when the structure has been determined, it is a static picture. A protein is a dynamic system, and understanding dynamics is important for understanding function.
My research is at the intersection of many disciplines, incorporating ideas from chemistry, biology, physics and computer science to model the movement of molecules as they interact with and move through the protein channel. Using mathematical equations, we can simulate the motion of all atoms in a molecule for about ten nanoseconds, which is a long time by computer simulation standards. Building on information obtained from this molecular model, we can create a hierarchical system of models to predict the movement of molecules, the movement of protein parts, and the function of the protein channel. We could then use this model as a way to determine how the channel’s 3D structure is related to its function.
What type of ion channels are you studying?
The two main ion channels I am currently studying are glutamate receptors and alpha-hemolysin.
Glutamate receptors
Glutamate receptors, found mostly in neurons, form an ion channel through the neuron’s membrane. Glutamate is a signaling molecule released by other neurons. It docks with the glutamate receptor, which causes a series of changes that eventually excite the neuron. Although the structure of the docking site is known, no one knows how the protein parts change to open the channel. I am starting by calculating the vibrations of glutamate when it attaches to the receptor. My goal is to develop a computer model to predict the chain of events leading from the docking of the glutamate molecule to the opening and closing of the channel.
Ultimately, we could use the model to design a drug to interfere with or help that process. For example, pharmaceutical companies may scan hundreds of potential drugs to find one that has the desired effect. Determining how drugs interact with the receptor in a computer model would save tremendous time and money in the drug development process. While we are not doing drug design in my lab, we are working toward developing models that may help with the process.
Alpha-hemolysin
Bacteria release a toxin, alpha-hemolysin, that kills cells by inserting into their membranes and forming channels that leak ions and other molecules. This bacterial protein is being studied as a prototype in the nanoscale engineering of chemical sensors. My group is using equations to calculate the electric current ions create as they move through the channel. We hope to understand how blocking the area inside the channel affects its current-conducting properties. Determining this structure/function relationship will allow us to construct nanoscale devices that mimic ion channels. Such devices could be used as biosensors to detect minute amounts of chemicals, such as a change in blood glucose levels or the presence of a harmful chemical in the air.
Are you collaborating with anyone here at Carnegie Mellon?
I have always been impressed with Carnegie Mellon’s interdisciplinary agenda and its focus on problem-solving. Because my interests are very interdisciplinary, Carnegie Mellon is a great place for me to find collaborators. I have already started to collaborate with the Pittsburgh Supercomputing Center and with Gordon Rule, associate professor of biological sciences here at Carnegie Mellon. We are collaborating with Mike Casio, assistant professor of biophysics at the University of Pittsburgh School of Medicine, and with my former scientific advisor and friend Rob Coalson, professor of physics and chemistry at the University of Pittsburgh, to study glycine receptor mechanisms. We’re also collaborating with Judith Klein-Seetharaman, an assistant professor of pharmacology at the University of Pittsburgh School of Medicine and a research scientist at Carnegie Mellon’s School of Computer Science.
Amy Pavlak
January 10, 2005
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