# Resonator Approach to Pulsed Dynamic Nuclear Polarization of Membrane Proteins

> **NIH NIH R01** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2021 · $258,524

## Abstract

Nuclear Magnetic Resonance (NMR) is an exceptionally versatile and informative spectroscopic technique for
atomic-level structure-function studies of biological macromolecules in their native-like environments. In
particular, solid-state NMR allows one to study membrane proteins in lipid bilayers under the conditions
approaching those encountered in the biological cells. Membrane proteins are of particular interest for
biomedicine being implicated in numerous biological processes and diseases and constituting nearly 50% of
the modern drug targets. However, low polarization of the nuclear spins limits NMR sensitivity and represents
the major roadblock for expanding its use in structural biology. Dynamic nuclear polarization (DNP) can
potentially boost sensitivity of NMR by up to several hundred times via irradiating the sample with mm-waves
at matching frequencies. Despite significant progress, DNP NMR of biological samples above the freezing
temperatures remains to be a challenge mainly because of short relaxation times of the nuclear and electron
spins at higher temperatures and excessive sample heating by mm-waves. We propose to overcome these
fundamental problems by constructing a novel 200 GHz/300 MHz DNP spectrometer which will be based on
resonant mm-wave structures and will operate in a pulse mode for DNP transfer vs. the continuous mode
currently in use. The key innovation is our recently invented mm-wave photonic band-gap resonators which
increase the sample volume by approximately 1-2 orders of magnitude as compared to the existing resonator
cavity designs. We propose to increase the quality factors of such resonators from Q=200 as demonstrated for
the prototype to at least Q=1,000 in order to boost mm-wave field at the sample. Achieving these higher mm-
wave fields will be essential for enabling advanced pulse schemes for DNP that will provide maximum NMR
signal enhancements while minimizing sample heating. The spectrometer development will be guided by
computer simulations of mm-wave fields and pulse DNP sequences, and will be based on the existing low-
power prototype operating in a continuous DNP mode yielding record-breaking preliminary data obtained at
room temperature. The spectrometer will operate over a broad temperature range (100-330 K), and multi-
resonance probeheads will be optimized for hydrated biological samples above the freezing point. The new
DNP technology will be applied to a series of biological samples including hydrated membrane proteins aligned
by nanoporous substrates. Success of the project will be built upon the extensive expertise of the two
collaborating PIs (Nevzorov and Smirnov) in designing and constructing a room temperature DNP NMR
spectrometer prototype based on solid-state mm-wave components. The new pulsed DNP spectrometer will
open up unexplored perspectives with regard to developing novel pulse methodologies for DNP-enhanced
solid-state NMR of membrane proteins. This is a high-gain high-risk proj...

## Key facts

- **NIH application ID:** 10242008
- **Project number:** 5R01GM130821-04
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Alexander A. Nevzorov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $258,524
- **Award type:** 5
- **Project period:** 2018-09-18 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242008

## Citation

> US National Institutes of Health, RePORTER application 10242008, Resonator Approach to Pulsed Dynamic Nuclear Polarization of Membrane Proteins (5R01GM130821-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10242008. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
