Three-Dimensional Structure of Biopolymers

Our concern in this section, however, is not the application to biopolymers of methods that are equally applicable to smaller molecules. Rather, we discuss here a totally different approach to the determination of precise three-dimensional structures of these molecules, in which NMR data play a key role. We illustrate the concept with proteins, which have yielded particularly useful information, but the general approach can also be used with nucleic acids and with complexes of a protein and a nucleic acid. 

There are three aspects to consider. First, we summarize briefly the underlying computational framework needed and the general strategy used in the structure determination. Second, we cover the use of 2D, 3D, and 4D methods to permit the sequential assignment of peaks to specific amino acids. Finally, we describe the use of nuclear Overhauser enhancements and spin coupling constants to provide restraints on interproton distances and bond angles, and we indicate how dipolar coupling and chemical shifts can sometimes add further information on molecular conformation. 

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NMR methods have also been used extensively to determine the configuration and conformation of both moderate-size molecules and synthetic polymers, whose primary molecular structure is already known. During the past decade high resolution NMR, particularly employing 2D and 3D methods, has become one of only two methods (x-ray crystallography is the other) that can be used to determine precise three-dimensional structures of biopolymers—proteins, nucleic acids, and their cocomplexes—and NMR alone provides the structure in solution, rather than in the solid state. 

In this chapter, we will describe the structure of the nucleic acids, DNA and RNA. We will first look at their building blocks, the nucleosides and nucleotides, and then describe how these building blocks are linked to form giant nucleic acid molecules. Later we will consider the three-dimensional structures of these vital biopolymers and how the information they contain (the genetic code) was unraveled. 

With respect to X-ray crystallography, improvements in instrumentation are now enabling organic chemists to carry out their own measurements to ascertain structures, for example, of synthetic intermediates. The most exciting advance, however, is seen in the field of biopolymers, where entire structures of enzyme-substrate complexes, clusters of proteins and reactive centers, etc., have been elucidated. In most cases, such achievements lead to quantum jumps in our understanding of intricate biochemical processes by defining the three-dimensional structures of all molecules involved. 

Imberty, A. Perez, S. (1988). A Revisit to The Three-dimensional Structure of B-amylose. Biopolymers, 27, 1205-1221. 

SCR (structurally conserved regions) sections of a biopolymer sequence that are identical to that of another sequence, for which there is a known three-dimensional structure... 

The Encyclopedia of NMR1 contains a very large number of articles on biological applications of NMR, including discussions of the methodology used for three-dimensional structure determination, along with presentations on individual biopolymers. 

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