Novel weak alignment techniques for nuclear magnetic resonance spectroscopy and applications to biomolecular structure determination

Nuclear magnetic resonance spectroscopy has continuously been developing ever
since its introduction as a structural method in bioscience. Recently established
residual dipolar coupling techniques yield information on long-range order in weakly
aligned samples as they define the orientation of vectors between nuclei in a common
global reference frame. These data complement classical short-range information and
have a unique potential especially for the characterization of non-globular states.
This thesis describes the development of novel methods for the weak alignment of
biomacromolecules in charged gels and for the measurement of long-range residual
dipolar couplings in perdeuterated proteins. These weak alignment techniques and
other nuclear magnetic resonance methods were applied to study the structure and
folding of various proteins such as the fibritin folding nucleus, the minicollagen
cysteine rich domain and human protein tyrosine phosphatase 1B.