Protein Dynamics in the Solid-State from 2H NMR Lineshape Analysis: a Consistent Perspective

• Published in: The journal of physical chemistry. B 2015-02, Vol.119 (7), p.2857-2868
• Main Authors: Meirovitch, Eva, Liang, Zhichun, Freed, Jack H.
• Format: Article
• Language: English
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/jp511386b

Deuterium lineshape analysis of CD 3 groups has emerged as a particularly useful tool for studying μs - ms protein motions in the solid-state. The models devised so far consist of several independently conceived simple jump-type motions. They are comprised of physical quantities encoded in their simplest form; improvements are only possible by adding yet another simple motion, thereby changing the model. The various treatments developed are case-specific; hence comparison amongst the different systems is not possible. Here we develop a new methodology for 2 H NMR lineshape analysis free of these limitations. It is based on the microscopic-order-macroscopic-disorder (MOMD) approach. In MOMD motions are described by diffusion tensors, spatial restrictions by potentials/ordering tensors, and geometric features by relative tensor orientations. Jump-type motions are recovered in the limit of large orientational potentials. Model-improvement is accomplished by monitoring the magnitude, symmetry and orientation of the various tensors. The generality of MOMD makes possible comparison amongst different scenarios. CD 3 lineshapes from the Chicken Villin Headpiece Subdomain, and the Streptomyces Subtilisin Inhibitor, are used as experimental examples. All of these spectra are reproduced by using rhombic local potentials constrained for simplicity to be given by the L = 2 spherical harmonics, and axial diffusion tensors. Potential strength and rhombicity are found to be ca. 2 − 3 [ k B T ]. The diffusion tensor is tilted at 120° from the C−CD 3 axis. The perpendicular (parallel) correlation times for local motion are 0.1 − 1.0 ms (3.3 − 30 μs). Activation energies in the 1.1 − 8.0 kcal/mol range are estimated. Future prospects include extension to the 2 H relaxation limit, application to the 15 N and 13 C NMR nuclei, and accounting for collective motions and anisotropic media.