Heteronuclear Relaxation and the Experimental Determination of the Spectral Density Function

Abstract

Proteins have always been known as dynamic molecules. With the success of X-ray crystallography in solving protein structures over the past thirty years, the static aspects of proteins have been emphasized, primarily because this technique can only characterize relatively rigid and completely folded proteins. On the other hand, NMR can study partially folded proteins and can characterize well internal motions. Among the most fruitful techniques to characterize internal mobility in proteins are relaxation time measurements, and a large number of studies have focused on that aspect recently (see e.g. Wagner, 1993). Globular proteins must undergo a range of motions in space and time to modulate the stunning array of critical biological processes such as enhance the rate of transcription of DNA, transport electrons, maintain structural integrity, or modulate cellular immune responses (McCammon & Harvey, 1985; Brooks et al., 1988). Understanding such motion inside a protein might thus provide some insight into their behavior. For example, it may allow the elucidation of the potential energy surface on which these proteins move, it may provide some clues on how they fold from a linear chain to three dimensional structure. Finally, dynamics is important in the context of structure refinement. Mobility studies can allow one to detect erroneously too tightly constrained structures, and identify regions that are rigid but appear artifactually disordered in structure calculations due to incomplete data analysis.