Tools of structural and computational biology will be used to uncover principles of biological recognition and assembly at the root of normal and pathological molecular complexes. The nature of the amyloid state of proteins, found in Alzheimer's and other neurodegenerative diseases, will be explored by x-ray diffraction and related methods. The primary goals will be learn the 3D structure of amyloid, which from preliminary experiments seems to be a dehydrated, hydrogen-bonded state. A second goal will be to understand the possible relationship of amyloid to the phenomenon of 3D domain swapping, found in other protein aggregates. In another line of work, computational methods will be extended for identifying the interacting networks of macromolecules in cells. Data from fully sequenced genomes will be basis of this work. Also structures of proteins will be determined that display interactions related to the general questions of recognition and assembly. One of these is glutamine synthetase, which may serve as an excellent target for a drug against tuberculosis.
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