L-04:NMR-Based Technologies for Analyzing Biomolecule Dynamics

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NMR-Based Technologies for Analyzing Biomolecule Dynamics
― Investigating Protein Interactions, 3D Structures, and Dynamics in Solution at Atomic Resolution ―

Tomohide Saio  Professor
Division of Molecular Life Sciences, Core Research Department, Institute for Advanced Medical Sciences
Keywords Protein structure, ligand binding evaluation, drug discovery technologies
Laboratory URL https://saio-lab.jp/eng/
Research Overview
● Biomolecular NMR Enables Reliable Analysis of Protein Structure and Dynamics in Solution, but Molecular Size Has Been a Major Limitation
Nuclear magnetic resonance (NMR) spectroscopy, which detects signals from atomic nuclei in molecules in solutions, enables highly reliable evaluation of protein structure, dynamics, and interactions. As such, NMR is an essential tool in the life sciences and drug discovery research fields. However, conventional solution-state NMR analyses have mainly been applicable to relatively small molecules (≤30 kDa). For many larger proteins, application has been challenging due to limitations in spectral resolution and sensitivity.

● Proposal of NMR Analysis for High-Molecular-Weight Proteins Using Selective Isotope Labeling and Paramagnetic Probe Methods
In this research, we employ techniques that enable selective stable isotope labeling of specific amino acids and functional groups in proteins, enabling the acquisition of high-sensitivity and high-resolution NMR signals even for high-molecular-weight proteins. In addition, by using paramagnetic probes, we propose methods to obtain long-range structural information that has been difficult to access with conventional NMR approaches.
These advances make it possible to perform structural and interaction analyses of proteins with molecular weights of several hundred kilodaltons, thereby overcoming the traditional size limitations of NMR.
 
Potential Applications and Commercialization Prospects
● Tools for Evaluating Intermolecular Interactions in Drug Discovery Research
NMR has long been utilized as a powerful tool for evaluating intermolecular interactions and three-dimensional structures in drug discovery research. With the present technology, the size limitations that have restricted the applicability of conventional NMR methods can be alleviated, enabling NMR analysis of larger proteins. This advancement is expected to facilitate the evaluation of weak molecular interactions and the structural analysis of dynamic protein complexes, thereby expanding the utility of NMR in drug discovery and related fields.

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Publications ● Saio T, Ishimori K. Accelerating Structural Life Science by Paramagnetic Lanthanide Probe Methods. Biochim Biophys Acta Gen Subj. 2020 Feb;1864(2):129332.
● Saio T, Kawagoe S, Ishimori K, Kalodimos CG. Oligomerization of a molecular chaperone modulates its activity. eLife. 2018 May 1;7:e35731.

Last updated date:October 15, 2026

 

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