External Media for Inducing Weak Alignment in Biomacromolecules

Abstract

Residual dipolar couplings (RDCs) or more generally residual tensorial couplings (RTCs) have allowed protein and other molecular solution structures to be defined at an accuracy and precision that rivals the best crystal structures, while additionally providing information on protein dynamics at submicrosecond to millisecond timescales, which are central to biological function. These benefits derive from the high sensitivity of the RTC measurement even for large molecules and the straightforward mathematical dependence of the RTC on the orientation of the local atom group relative to a common molecular reference frame. A prerequisite for observing RTCs at high sensitivity in solution is a suitable second-rank molecular orientation, which deviates on the order of 10−4–10−3 from isotropy. While in favorable cases such orientations may be obtained via the intrinsic magnetic anisotropy of molecules, the addition of small amounts of orienting substances to the liquid medium provides a simple, general mechanism to achieve suitable orientation for RTC measurements for all classes of solute molecules. In this chapter, we describe the theory of rotational ordering and the practical aspects of using external orienting substances for the measurement of RTCs.