Presented here is a new approach for the elucidation of the dynamics and structure of membrane bound proteins and polypeptides with atomic resolution that is based on solid state Nuclear Magnetic Resonance experiments. The structural aspects of the effort result from determining the orientation of covalent bonds within the polymerws with respect to a common axis, the magnetic field direction. From the bond orientations of adjacent groups the torsion angles are determined defining the relative orientation of these groups. The dynamic characterization is composed of two parts; first a spatial characterization of the motion, defining the axis about which the motion occurs, the type of motion whether it is diffusional or discontinuous as in flip motions between two potential minima, and finally the amplitude of the motion. Only when this spatial model for the motion is complete can an accurate determination of the frequency of the motion be made from the NMR data. To demonstrate the validity of this approach for determining structure and dynamics and to answer many biophysical questions concerning the function of the Gramicidin A cation channel at an atomic level this molecule will be studied. The ion transport characteristics of the channel have been extensively studied in the several laboratories. These results show that the Gramicidini channel may be a very useful model for the proteinaceous Na+ and K+ channels of higher organisms. The folding motiff for the polypeptide backbone is generally accepted as that of the original channel model. However, the structural details are unresolved at this time and the magnitude of the structural distortions that take place upon binding ions is not known. Structural studies have been hindered both by the extreme sensitivity if this molecule to its solvent environment and by the difficulty of forming cocfrystals of Gramicfidin and lipid which will diffract to high resolution. Furthermore, the dynamics of the atoms in the polypeptide backbone which presumably coordinate the unhydrated ions during passage through the channel are uncharacterized. With both a detailed structural and dynamic picture of Gramicidin unprecedented correlations between structure, dynamics and function will be achieved.
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