The Department of Biomedicine

BBB seminar: Robert H. Kretsinger

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Ab initio prediction of protein structure

Robert H. Kretsinger
Department of Pharmacology, University of Virginia, Charlottesville, VA, USA

The sequences of hundreds of millions of bases of nucleic acids are determined daily around the world and the amino acid sequences of hundreds of proteins deduced. Many of these amino acid sequences are recognized as homologs of proteins of known structure. This trove of sequence and structure information has provided valuable insights into cell function, disease, development, and evolution. Most important, this information allows us to pose new, focused questions for research. Structure determination, however, is expensive and lags behind sequence determination. Much more information would be available if a three dimensional structure accompanied every new protein sequence. I summarize preliminary results, comment on the state of the art, and outline a strategy to break the "second half of the genetic code", i.e. to understand how the structure of a protein is encoded in the amino acid sequence.

Host: Anni Vedeler, Department of Biomedicine

Prof. Robert Kretsinger, who received his Ph.D. in Biophysics from M.I.T. in 1964, has had a long-standing interest in calcium and calcium binding proteins. He has determined the structures of calmodulin and several other calcium-binding proteins containing EF-hand domains, as well as the structure of annexin IV which has a different type of calcium-binding site. His finding that calmodulin consists of two globular domains connected by a highly flexible linker region was published in Science in 1992. Furthermore, Robert Kretsinger has grown and characterised several two dimensional crystals of both protein kinases Cδ and β as grown on phospholipid monolayers. Recently, he has initiated a knowledge based program to predict ab initio the tertiary structures of proteins from their amino acid sequences. This was done in collaboration with Sven Hovmöller (Stockholm University, Sweden) and Roger Ison (Mantic Software Corporation, Loveland, CO, USA). Robert Kretsinger's dedication to structures is reflected in the sculptures he creates (http://www.virginiastonecarversguild.com/view_profile.php?id=9).