Nuclear Magnetic Resonance and Optical Studies of Polypeptide Chain Conformation

Abstract

Everyone is aware of the intense effort that has been devoted to the study of the structure of proteins and polypeptides during the last two decades, culminating in the complete x-ray determination of the structures of myoglobin, hemoglobin, lysozyme, and ribonuclease. Few problems in natural science have been subjected to such a heavy assault with such a variety of weapons. The most important of these, of course, has been x-ray diffraction. One cannot imagine at present any other technique capable of providing the thousands upon thousands of individual parameters necessary to describe a complete protein structure. In view of the spectacular triumphs of this method, why do many of us who are concerned with polypeptide and protein structure continue to employ such relatively humble techniques as optical rotation, circular dichroism, and nuclear magnetic resonance, which are capable of giving at most only a handful of structural parameters ? I think there are good answers to this question, and I would suggest a few as follows:

• (a) If our main interest is in polypeptides of a single repeating residue, then only a relatively limited number of molecular parameters may be adequate for a good description.

• (b) X-ray studies are limited for the most part to crystalline solids and, except in certain special circumstances, cannot inform us what bio-polymers are doing in solution. (One such exception is the x-ray study of polypeptides in solution by Brady, Salovey and Reddy1 in our laboratories; this requires labelling with heavy atoms such as bromine.)

• (c) Optical and n.m.r. methods have an intrinsic interest in their own right. This may be the most important reason for using them.