The Exact Nuclear Overhauser Enhancement: Recent Advances

Molecules

Alexandra Born¹  Morkos A. Henen¹  Parker J. Nichols¹  Beat Vögeli¹  Simon Olsson²  Celestine N. Chi³  Peter Güntert⁴  Julien Orts⁴  Dean Strotz⁴ 

[1] Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, 12801 East 17th Avenue, Aurora, CO 80045, USA;Department of Mathematics and Computer Science, Freie Universität Berlin, Arnimallee 6, Berlin 14195, Germany;Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, Uppsala SE-75123, Sweden;Laboratory of Physical Chemistry, ETH Zürich, ETH-Hönggerberg, Zürich 8093, Switzerland;

关键词: NMR;    biological macromolecules;    proteins;    dynamics;    correlated dynamics;    exact NOE;    structure calculation;    structure ensemble;    allostery;    conformational space;   

DOI  :  10.3390/molecules22071176

来源: DOAJ

【 摘 要 】

Although often depicted as rigid structures, proteins are highly dynamic systems, whose motions are essential to their functions. Despite this, it is difficult to investigate protein dynamics due to the rapid timescale at which they sample their conformational space, leading most NMR-determined structures to represent only an averaged snapshot of the dynamic picture. While NMR relaxation measurements can help to determine local dynamics, it is difficult to detect translational or concerted motion, and only recently have significant advances been made to make it possible to acquire a more holistic representation of the dynamics and structural landscapes of proteins. Here, we briefly revisit our most recent progress in the theory and use of exact nuclear Overhauser enhancements (eNOEs) for the calculation of structural ensembles that describe their conformational space. New developments are primarily targeted at increasing the number and improving the quality of extracted eNOE distance restraints, such that the multi-state structure calculation can be applied to proteins of higher molecular weights. We then review the implications of the exact NOE to the protein dynamics and function of cyclophilin A and the WW domain of Pin1, and finally discuss our current research and future directions.

【 授权许可】

Unknown