Protein dynamics investigated by neutron diffraction.

Abstract

The most correct model of the molecular structure of a protein molecule is one which describes it as having a number of variable conformational states. These states differ in degree over a large spectrum of structural variation ranging from individual atomic vibrational motion to significant tertiary denaturation. The application of the neutron diffraction techniques discussed above dealt with two classes of conformational fluctuation, "protein breathing" and "regional melting." The utility of the neutron technique stems from the ability to locate hydrogen atoms and to discriminate between hydrogens and deuteriums. This latter attribute allows for performing H/D exchange experiments by identifying individual sites of exchange. With this information it has been possible to discern which regions of the protein molecule undergo regional melting. Protein breathing was explored by analyzing the rotational properties of side chain methyl groups. Such information clearly suggested that most of these groups reside in "staggered" (low energy) conformation in the time averaged structure and are not greatly affected by local structural packing. Together these two classes of conformational fluctuation span nearly the full range of all motions that might play a role in biological activity. Information about such motions can be obtained from other types of physicochemical methods, but in most cases the interpretation of the data is considerably less definitive than that which can be obtained from a neutron analysis.