Biomolecular NMR: Structure and Molecular Recognition

Catalog description

Prerequisite: 16268 Protein Chemistry: Principles Nuclear magnetic resonance spectroscopy (NMR) is a powerful tool for the interrogation of biomolecular structure and interactions at atomic resolution. Structural genomics efforts have produced refinements in the methodology for three-dimensional protein structure determination, such that new structures can be solved in a matter of weeks using increasingly automated processes. This course begins with a description of the quantum mechanical basis for multidimensional NMR using the product operator formalism. This powerful operator algebra rigorously predicts the propagation of the nuclear spin wavefunction under a time- independent Hamiltonian operator governing interactions between nuclear spins and between spins and static or transient magnetic fields, enabling the development of increasingly complex pulse sequences for multidimensional, multinuclear NMR measurements of biomolecules. Simple pulse sequences for magnetization transfer and isotope editing are described using product operators and combined into more complex two- and three- dimensional pulse schemes for triple- resonance correlation of nuclei in proteins. Systematic application of these NMR methods to the sequence-specific assignment of isotopically enriched proteins will then be linked to the interpretation of other of types of NMR data (nuclear Overhauser effect; scalar and dipolar couplings) that report directly on tertiary structure. The balance of the course will consist of practical, hands-on training in basics of 2D/3D NMR data acquisition, processing, and analysis, as well as interactive computer tutorials on the chemical shift assignment and 3-D structure determination processes.