# UVPD Mass Spectrometry of Protein Complexes

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2020 · $314,087

## Abstract

Abstract. Protein interactions mediate cellular communication, signaling, and numerous other cell
functions. Recognition of these interactions has inspired much of the activity in the field of drug discovery
in the context of designing inhibitors to selectively bind and disrupt the functions of protein targets. The
drug discovery process faces new challenges with the growing threat of drug-resistant strains of
pathogens and the search for more specific therapeutics to fight cancer. Breakthroughs have been
propelled by progress in the understanding of cell biochemistry as well as technological advances in
biophysical methods that facilitate the characterization of protein interactions and structures of complexes.
This proposal focuses on the development of ultraviolet photodissociation (UVPD) in conjunction with
native-spray mass spectrometry as an innovative strategy for analysis of protein complexes. The
identification and characterization of protein-ligand and protein-protein complexes offers the opportunity
to provide insight into protein function at a molecular level and accelerate drug discovery. The objectives
of this proposal include:
Aim 1: Development of UVPD for examining protein-ligand complexes. We will develop robust
native-spray/UVPD-MS strategies to create conformational maps of protein-ligand complexes governed
by different binding modes. The classes of ligands will include substrates, cofactors, and inhibitors.
Aim 2: Integrating separation methods with UVPD-MS for higher throughput analysis of protein
complexes. To expand the versatility of the UVPD-MS strategy, we will adapt it for a higher throughput
workflow via integration with size exclusion chromatography (SEC). Front-end SEC will make sample
introduction reproducible and automated, thus making it better suited for quantitative applications.
Aim 3. Extending UVPD-MS for protein-protein complexes. Many proteins exist and function as part
of multimeric complexes, thus motivating our interest in extending UVPD-MS methods for characterization
of protein-protein and protein-protein-ligand complexes.
Aim 4: Application of UVPD-MS methods for key biological problems. The methods developed in
Aims 1 – 3 will be utilized to attack a number of high impact biological problems via collaborations with
research groups in molecular biology, biochemistry, and medicinal chemistry. These collaborative
problems encompass three themes: development of protein inhibitors as drugs, unravelling the influence
of point mutations on protein structure, and deciphering how protein-protein interactions modulate activity
and function.

## Key facts

- **NIH application ID:** 9873044
- **Project number:** 5R01GM121714-04
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Jennifer S. Brodbelt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $314,087
- **Award type:** 5
- **Project period:** 2017-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873044

## Citation

> US National Institutes of Health, RePORTER application 9873044, UVPD Mass Spectrometry of Protein Complexes (5R01GM121714-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9873044. Licensed CC0.

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