Two-Dimensional (2D) NMR Methods

12 TROSYPrinciples and Applications

Harindranath Kadavath^1,2 and Roland Riek^1,*

¹ Laboratory of Physical Chemistry, ETH Zurich, Switzerland² Department of Structural Biology, St Jude Children’s Research Hospital, Memphis, TN, USA^* Corresponding Author

12.1 Introduction

Nuclear magnetic resonance (NMR) spectroscopy is a powerful and versatile experimental tool in structural and molecular biology, that allows the structure determination of biomolecules, study of biomolecular interactions and dynamics at atomic-resolution and near-physiological conditions. Understanding the structure-dynamics-function paradigm of biomacromolecules requires high quality data. Structural biology is an emerging area of research with developments in the technical and experimental methods used. In the early phase of structural studies, all atomic-resolution structures of biomolecules were solved either by X-ray diffraction of single protein crystals or by NMR in solution [1, 2]. Recently the revolution in the field of cryo-electron microscopy single particle analysis provided an alternative to X-ray crystallography for large (>100 kDa) molecules with significant gain in resolution [3, 4]. Progress in solid-state NMR methods enabled the determination of high-resolution 3D structures of amyloid fibrils at atomic resolution [5, 6]. Although the developments in multidimensional NMR methods allowed the structure determination of small proteins with size up to ∼30 kDa, it is harder to achieve high-quality ...