# Visualizing chemical bonding in biological macromolecules by microcrystal electron diffraction

> **NIH NIH R21** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2020 · $196,250

## Abstract

SUMMARY
Methods and techniques capable of directly visualizing chemical bonding and charge in biomolecules would add
an exciting tool to the field of structural biology. Unlike X-rays, electron diffraction is very sensitive to the bond-
charge distribution, especially at lower resolution and small scattering angles, so that electron diffraction has
been used on inorganic samples to study and image the charge distribution in chemical bonds, directly mapping
out both covalent and ionic bonds. This sensitivity is readily apparent from the large difference between tabulated
electron scattering factors for atoms and those for ions. The overall aim of this project is to develop and extend
charge-cloud modeling methods to biomolecular structures and couple these procedures with microcrystal
electron diffraction (MicroED) data collection and processing for the direct determination of chemical bonding in
high-resolution biomolecular structures. The charge-cloud method was initially developed to determine the
bonding in an organic small molecule phthalocyanine and used transmission electron diffraction patterns from
thin crystals. It was shown that by properly treating electron diffraction data with this method, charge density in
the bonds between atoms could be seen in a 2D projection of the organic molecular structure. To extend this
method to 3D structures of biological molecules, high-quality 3D electron diffraction data will be required.
Therefore, we will make use of the MicroED method for electron diffraction data collection on several model
microcrystalline samples. Since its development, MicroED has been shown to produce high-quality electron
diffraction data that yields high-resolution 3D structures of biological molecules. The combined method of
MicroED data collection and processing along with charge-cloud refinement of low order Bragg reflections will
yield a straightforward, efficient, widely accessible technique for the direct visualization of bonding in biological
samples.

## Key facts

- **NIH application ID:** 10020791
- **Project number:** 5R21GM135784-02
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Brent Nannenga
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,250
- **Award type:** 5
- **Project period:** 2019-09-20 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020791

## Citation

> US National Institutes of Health, RePORTER application 10020791, Visualizing chemical bonding in biological macromolecules by microcrystal electron diffraction (5R21GM135784-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10020791. Licensed CC0.

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