# High-Throughput Assessment of De Novo Protein Design: Generation of Molecular Probes for Guanine Exchange Factors

> **NIH NIH F32** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $65,310

## Abstract

Knowledge of the underlying principles of protein-protein interactions facilitates the design of
proteins with novel functions that remain unobserved in nature and create new opportunities for
scientists to dissect the molecular basis for diseases. Although significant advancements in the
field have been made, evaluation of the computational design process by expressing proteins in
vitro has been limited to small sample sizes due to constraints associated with gene synthesis.
Recent advances in the field of oligonucleotide synthesis have enabled the high-throughput
screening of designs with yeast display. We will harness this technology to assess new methods
for packing amino acids at protein interfaces and to determine ideal score term targets for
designed models. During this process, we will develop proteins that inhibit guanine exchange
factors (GEFs), which are critical for cellular proliferation and have thereby garnered significant
interest as therapeutic targets for cancer. We also aim to develop novel biosensors that are
capable of reporting GEF activation by engineering a binding site into the SnapTag and HaloTag
constructs. These results are expected to have an important positive impact for the field of
protein engineering, ultimately providing new opportunities for the development of reagents that
enable the scientific community to advance our understanding of biological processes.

## Key facts

- **NIH application ID:** 9911096
- **Project number:** 1F32GM136112-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** David Thieker
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 1
- **Project period:** 2020-01-09 → 2021-01-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9911096

## Citation

> US National Institutes of Health, RePORTER application 9911096, High-Throughput Assessment of De Novo Protein Design: Generation of Molecular Probes for Guanine Exchange Factors (1F32GM136112-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9911096. Licensed CC0.

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