McGowan Institute for Regenerative Medicine
affiliated faculty member Ivet Bahar, PhD (pictured), is the John K. Vries chair and professor in the Department of Computational & Systems Biology at the University of Pittsburgh, and an associate director of the University of Pittsburgh Drug Discovery Institute (UPDDI). UPDDI is committed to identifying small molecules that can be used as chemical probes for biological activities and as leads for new therapies for human diseases.
The UPDDI uses the latest advances in scientific understanding of cell signaling processes and disease states, laboratory automation and compound storage/retrieval, data management, combinatorial chemistry and diversity-oriented synthesis as a foundation for its drug discovery efforts. The Institute is a model of collaboration, comprising faculty members from three schools at the University of Pittsburgh. UPDDI balances academic research flexibility with industrial compound screening and development efficiency. Research efforts at UPDDI were highlighted recently by Reid R. Frazier in the Summer 2011 PittMed magazine.
Mr. Frazier reports on high throughput screening by the pharmaceutical industry and its current limitations. Modern imaging, chemistry, and genetics have made drug discovery—whether through plant- and mineral-derived or synthetic compounds—much, much faster, but the process remains riddled with pitfalls.
“The old paradigm was one drug, one target, one disease,” says Dr. Bahar. “You look for a specific drug targeting a specific protein. It’s widely understood this paradigm is invalid.”
In Dr. Bahar’s lab, scientists create computer models for protein movement. Parts of proteins, called domains, can act like spring-loaded door hinges. During cell signaling, they can swing open or slam shut. Each position alters the activities of the protein. In the digital movies she and her collaborators have made to model protein movement, proteins look like balls of yarn and ribbon, bobbing up and down underwater. The models help predict a protein’s “druggable sites” for which a chemist can design a compound.
In Mr. Frazier’s article, Dr. Bahar says her group can predict internal motion in a protein in the same way one can predict how a door hinge or human elbow moves. “These are motions that the structure favors. Its structure has evolved to favor particular motions that are needed for its function,” she says. “This is evolutionary selection.”
Dr. Bahar is also the founding director of the Carnegie Mellon-University of Pittsburgh PhD Program in Computational Biology, and the Center for Computational Biology & Bioinformatics, School of Medicine, University of Pittsburgh.
Illustration: McGowan Institute for Regenerative Medicine.
PittMed Summer 2011
Bio: Dr. Ivet Bahar
The Bahar Lab