Poster abstracts
Poster number 29 submitted by Gregory Jameson
Computational methods for obtaining quantitative biophysical parameters from NMR data
Gregory Jameson (Biophysics Graduate Program), Rafael Bruschweiler (Department of Chemistry and Biochemistry, The Ohio State University )
Abstract:
Biomolecular solution NMR experiments, such as spin relaxation, relaxation dispersion, and related experiments have consistently proven to be a rich source of quantitative dynamics and kinetics of biomolecules for elucidating their function at atomic detail. However, these experiments may require several days to perform, potentially making them time-prohibitive for certain applications. We introduce absolute minimal sampling of intensities (AMSi), a method that utilizes prior knowledge about a spectrum to determine how to design and process NMR experiments that are substantially faster than traditional methods. AMSi is used to characterize the structural dynamics of protein Im7 using chemical exchange saturation experiments (CEST). By comparison to traditionally sampled data we find that AMSi can obtain accurate results while increasing the speed of the experiment by up to 60-fold.1
Furthermore, although the traditional theory for analyzing NMR dynamics experiments is well established, this traditional theory requires several assumptions that may be violated in potentially valuable experiments. One system that violates these traditional assumptions is the transient interaction of biomolecules with large bodies, such as nanoparticles or static walls, especially when binding and unbinding occur on an intermediate timescale of around 104 s-1 encountered in practice. We present a unified framework for analyzing such data based on the stochastic Liouville equation (SLE), which is valid for large binding partners and regardless of the kinetics of binding/unbinding.2 Application of this theory demonstrates how relaxation can be significantly impacted by the kinetics of binding. It is further shown that when binding occurs on such timescales, transverse spin relaxation is able to report on internal dynamics that can be biologically relevant but are far slower than observable by traditional spin relaxation experiments.
References:
[1] Jameson G.; Hansen, A. L.; Li, D.; Bruschweiler-Li, L.; Brüschweiler, R. Extreme Nonuniform Sampling for Protein NMR Dynamics Studies in Minimal Time. J. Am. Chem. Soc. 2019, 141, 42, 16829–16838
[2] Jameson G.; Brüschweiler, R. NMR Spin Relaxation Theory of Biomolecules Undergoing Highly Asymmetric Exchange with Large Interaction Partners. J. Chem. Theory Comput. 2021
Keywords: NMR, nanoparticle, spin relaxation