Insight into Protein Interfaces May Aid Drug Design

BALTIMORE, MD – An experimental breakthrough by Dr. Roy Mariuzza and colleagues from UMBI’s Center for Advanced Research in Biotechnology (CARB) W.M. Keck Laboratory for Structural Biology and the National Cancer Institute at Frederick Cancer Research and Development Center, yields insight into the basic principles that govern the binding of proteins to one another—interactions that play a fundamental role in nearly every cellular process. The paper, entitled "Magnitude of the Hydrophobic Effect at Central versus Peripheral Sites in Protein-Protein Interfaces" was published in the February 2005 issue of the journal Structure, and is based in part on research funded by the National Institutes of Health.

The recently published findings may aid in the quest for drug inhibitors that specifically interrupt protein-protein complexes that underlie disease, an effort that has so far proven difficult. Protein interfaces consist of a central cluster of “hot spot residues” surrounded by components with a lesser role in binding. To explore that pattern, the researchers estimated the degree to which the central core repels water, or its “hydrophobicity.” Core interface components are more than twice as hydrophobic as elements at the periphery, they found, suggesting that stable protein binding relies on the formation of a water-tight seal surrounding central, interacting elements. The report further notes synthetic compounds that mimic this design might therefore serve as useful therapeutic inhibitors of protein interaction.

“This is absolutely biology on the edge; research that typifies the exciting molecular structure-function programs that CARB is so well known for throughout the world,” said Dr. Jennie Hunter-Cevera, President of UMBI. “The results from this paper will have a positive influence on applied drug discovery research.”

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Celebrating our 20th anniversary year, UMBI is the first and only biotechnology research institute within the University System of Maryland and was established in 1985. The University of Maryland Biotechnology Institute (UMBI) consists of five major research and education centers and is dedicated to advancing the frontiers of biotechnology. UMBI’s centers of research include: CARB, the Center for Advanced Research in Biotechnology located in Rockville; CBR, the Center for Biosystems Research located in College Park; and COMB, the Center of Marine Biotechnology, MBC, the Medical Biotechnology Center, and IHV, the Institute of Human Virology, all located in Baltimore. For more information, visit www.umbi.umd.edu