Three-dimensional molecular structures in solution

By far the deepest and most impressively detailed advance of biology by NMR has been its use to determine three-dimensional molecular structures in solution of proteins, polynucleic acids and even polysaccharides. This molecular level of understanding has helped explain at the molecular level how certain enzymes promote their very specific bond breakings or makings, how cancer agents intercalate with DNA, how inhibitors bind to enzymes and a host of other biological phenomena. 

Polyphemusin I, a defensive agent of the Atlantic horseshoe crab (Umulus polyphemus), is an antimicrobial peptide composed of 18 amino acids with two cystine crosslinks. The amino sequence is readily determined to be RRWCFRVCYRGFCYRKCR-NH2 by standard degradation techniques, but in order to understand the mechanism of how polyphemusin I kills bacteria, one needs to know the specific details of how it interacts with the membrane and other molecular parts of the cell. This molecule is specifically 

Importantly this structure reveals a cationic cleft in the molecule which would greatly aid in attaching this antimicrobial agent to phosphate moieties on membranes. While the determination of the mechanism is not complete, this study makes it clear how important it is to have full structures of molecules. 

From these few examples it is clear that NMR has a very wide applicability in terms of nucleus observed or molecule or system studied. The reader is urged to expand this horizon with the material in the suggested Further Reading and to imagine variations on any one of the above examples for new applications. 

Gerendas, J. and Ratcliffe R.G. (2000). Intracellular pH regulation in maize root tips exposed to ammonium at high external pH. J. Exp. Bot. 512 207-219. 

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