# Development of high-dose time-resolved X-ray footprinting technologies to enable detailed structural and kinetics information to be obtained for challenging biological problems

> **NIH NIH R01** · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · 2022 · $425,897

## Abstract

Abstract
The overarching goal in this project, both in the funded award and in this renewal, is to advance the
structural biology method of X-ray footprinting mass spectrometry (XFMS) in capability and accessibility
such that it becomes a premiere biophysical tool for biomedical investigators around the country. XFMS
is a solution state method used to map solvent accessible regions in macromolecules on a timescale of
microseconds, yielding information on conformation, protein-protein dynamics, and bound water
location and dynamics. It has been used to obtain useful structural information on a diverse range
biological systems, from small proteins to large complexes, as well as membrane proteins, and for
mapping interaction regions in antibody-target complexes. As part of the original award, we made
substantial progress towards our main goal by developing a unique high-throughput and automated
XFMS instrument, enabling use of the method to researchers nationwide. In this proposed renewal, we
plan to build on this success to implement new capabilities in keeping with the original goal of the grant.
Specifically, we plan to integrate fluorescence and Raman spectroscopies, fast mixing with jet delivery
capability, and size exclusion directly inline with the XFMS instrument. The integration of these
technologies into the XFMS instrument will enable even more challenging biological systems to be
studied using the method. While the new specific aims are ambitious, they build naturally from our
proven track record in developing complex instrumentation and the successful research team we built
during the first grant period. Proof of principle for these technologies is presented, along with
preliminary data, and the proposal outlines the significant technical challenges involved and how they
will be overcome. The resulting technologies will be a significant gain to the biomedical research
community and will be used to meet the increasing demand for access to the XFMS method.

## Key facts

- **NIH application ID:** 10446793
- **Project number:** 2R01GM126218-05A1
- **Recipient organization:** UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
- **Principal Investigator:** CORIE Y RALSTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $425,897
- **Award type:** 2
- **Project period:** 2018-01-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10446793

## Citation

> US National Institutes of Health, RePORTER application 10446793, Development of high-dose time-resolved X-ray footprinting technologies to enable detailed structural and kinetics information to be obtained for challenging biological problems (2R01GM126218-05A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10446793. Licensed CC0.

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