Session TOG. There are 3 abstracts in this session.

Session: COMPUTATION/THEORY 1, time: 4:00 - 4:25 pm

Computer Assisted 3D Structure Elucidation (CASE-3D) Using Isotropic and Anisotropic NMR Parameters for the Structural Analysis of Small Molecules

Roberto R. Gil
Carnegie Mellon University, Pittsburgh, PA

A multiNMR parameters fitting methodology called CASE-3D (Computer Assisted 3D Structure Elucidation) will be presented. The method performs configuration/conformation selection using Chemical Shifts, J Couplings, NOE-derived distances, Residual Dipolar Couplings (RDCs) and Residual Chemical Shift Anisotropies. This tool has been succesfully applied to the structural analysis of small molecules in Organic Synthesis, Natural Products and Medicinal Chemistry.

Session: COMPUTATION/THEORY 1, time: 5:05 - 5:20 pm

Low-Field NMR Spectroscopy with Spin-Lock Induced Crossing

Stephen DeVience
Scalar Magnetics, LLC, Cuyahoga Falls, OH

Proton NMR spectroscopy of organic molecules at low magnetic fields typically produces only a single spectral line devoid of identifying information, making it unsuitable for most analytical purposes. This study demonstrates an alternative form of spectroscopy using SLIC (spin-lock induced crossing). It shows that J-coupling spectroscopy can be performed on most organic molecules without the typical need for a heteronucleus. Based on the location and strength of spectral dips that occur at level anti-crossings during weak spin-locking, 1D and 2D spectra can be acquired and used to identify molecules whose conventional NMR spectra at low field appear indistinguishable. Simulations of spin chains, halogenated benzenes, and other molecules finds complex J-coupling spectra promising for spectral fingerprinting.

Session: COMPUTATION/THEORY 1, time: 5:20 - 5:35 pm

Spin Relaxation and Molecular Dynamics Simulations Reveal a Synergistic Relationship Between Water Dynamics and Functional Motions in Intrinsically Disordered Proteins

Nicola Salvi; Wiktor Adamski; Anton Abyzov; Malene R. Jensen; Martin Blackledge
Institut de Biologie Structurale, Grenoble, FR

Solvent plays a fundamental role in determining protein dynamics. In particular, functional dynamics of intrinsically disordered proteins (IDPs) depends crucially on their molecular environment.

Using 15N spin relaxation measurements and temperature-dependent molecular dynamics simulations, we derive a unified description of IDP dynamics under near-physiological conditions. We show that dynamics is highly dependent on the lifetime of hydrogen bonds formed by water molecules, suggesting that biomolecules and hydrotropes, which are present in physiological conditions and modulate the plasticity of hydrogen bond networks, also modulate IDP dynamics.

Indeed, we use 15N  relaxation measurements at multiple temperatures and crowding concentrations to develop a model of protein motions as a function of temperature and solvent friction and apply it to in-cellulo 15N relaxation rates, providing an accurate assessment of functionally important IDP dynamics in physiological environments.