Lecture 5

Macromolecular structure determination by NMR spectroscopy

Aims

• To introduce some of the concepts in macromolecular NMR spectroscopy.
• To raise some of the issues that structural bioinformaticians should be aware of when working with structures determined by NMR spectroscopy.

Objectives

After this lecture you will be able to:

• describe what kind of information can be obtained from proton NMR experiments, including COSY, TOCSY and NOESY experiments;
• discuss the calculation of ensembles of structures using restraints from NMR experiments;
• implement a method for clustering ensembles of structures;
• implement a method for detecting structurally conserved cores in an ensemble of structures.

Supplementary Material

Some of the lecture slides are available on-line (1 per page, 4 per page).

Wikipedia has an overview of nuclear magnetic resonance spectroscopy of proteins.

In the lecture I show Figure 3 and Table 1 from: Summers M.F. et al., 1992 (doi:10.1002/pro.5560010502). Figure 3 shows part of a NOESY spectrum; Table 1 mentions how many structural restraints of different kinds were used in solving a structure.

A method for clustering structures is described in:

Kelley, L.A., Gardner, S.P. and Sutcliffe, M.J. (1996) An Automated Approach For Clustering An Ensemble Of NMR-Derived Protein Structures Into Conformationally-Related Subfamilies. Protein Engineering, 9, 1063-1065. doi:10.1093/protein/9.11.1063

A computational method for detecting structurally conserved cores in an ensemble of structures is described in:

Kelley, L.A., Gardner, S.P. and Sutcliffe, M.J. (1997) An automated approach for defining core atoms and domains in an ensemble of NMR-derived protein structures. Protein Engineering, 10, 737-741. doi:10.1093/protein/10.6.737