# M. Hong RT&D

> **NIH NIH P41** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $56,041

## Abstract

Project Summary of TR&D 2 – High-field and fast-MAS SSNMR methods for biomolecular
structure and dynamics (PI: Hong)
 TR&D 2 seeks to develop new solid-state NMR technologies to determine protein structure
and dynamics and to produce isotopically labeled cholesterol for membrane protein structural biology.
Modern solid-state NMR based structure determination approaches focus on 13C and 15N based
resonance assignment and distance measurements. However, the low gyromagnetic ratios of 13C and
15N limit the measurable distances to less than ~8 Å, which makes it difficult to determine protein
three-dimensional folds and quaternary structures. Aim 1 of this TR&D is to overcome this bottleneck
in structure determination by developing 19F-based MAS NMR techniques to measure 19F-19F, 19F-13C
and 19F-1H distances, potentially to 2 nm. These experiments will be developed for high field and fast
MAS conditions to achieve the high-resolution and sensitivity necessary for structure determination.
The impact of 19F chemical shift anisotropy on dipolar recoupling will be investigated systematically.
Aim 2 of this TR&D is to develop 13C-2H correlation NMR techniques to measure protein dynamics at
high magnetic fields with higher angular sensitivity than before. This aim addresses the limitation of
13C-1H and 15N-1H dipolar-coupling based techniques, which are increasingly less sensitive to small-
amplitude motions as the magnetic field strength and MAS frequency increase. We will harvest the
power of the large 2H quadrupolar coupling for sensing molecular orientations by developing robust
polarization transfer techniques between 2H spins and 13C or 15N spins, so that we can measure 13C
and 15N resolved 2H quadrupolar spectra. In aim 3 of this TR&D, we will develop biosynthetic methods
for high-yield production of 13C and 2H-labeled cholesterol for membrane protein structural biology. By
partnering with four driving biomedical projects, we will test and deploy the technologies in this TR&D
to address outstanding biological questions in the areas of membrane proteins and cell walls.

## Key facts

- **NIH application ID:** 9933951
- **Project number:** 5P41GM132079-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Mei Hong
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $56,041
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933951

## Citation

> US National Institutes of Health, RePORTER application 9933951, M. Hong RT&D (5P41GM132079-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9933951. Licensed CC0.

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