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Program in Macromolecular Structure, Motion, Control

$1,610,886P01FY2006GMNIH

Yale University, New Haven CT

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Abstract

[unreadable] DESCRIPTION (Provided by the applicant): The objective of this Program is the development of a fundamental, i.e. physical and chemical, understanding of biological macromolecules such as proteins and catalytic RNAs, and of macromolecular assemblies such as the ribosome, the cytoskeleton, and the plasma membrane. Over the next five years RNAs, ribonucleoproteins, enzymes involved in gene expression, proteins that regulate gene expression, and membrane proteins will be emphasized. The primary experimental techniques used will be single crystal X-ray diffraction, and X-ray scattering. This Program will also foster studies of the motions that occur both within biological macromolecules, and between components of macromolecular assemblies as they function. Motion can be inferred from conformational differences between time-average structures determined for a macromolecule under different environmental conditions, or in different states of ligation. Of special interest are the motions that occur during the catalytic cycles of RNA and DNA polymerases and other enzymes, in the course of protein synthesis as the ribosome proceeds through its elongation cycle, as ion transporters function, and during the insertion of intrinsic membrane proteins into lipid bilayers and the passage of secreted proteins through membranes. Theoretical investigations will also be undertaken of protein-membrane interactions. [unreadable] [unreadable] [unreadable]

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