# EXPLORING STRUCTURE AND SEQUENCE SPACES OF G PROTEIN-COUPLED RECEPTOR SIGNALING

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $327,684

## Abstract

Abstract
Signaling across biological membranes is critical to living cells and involves membrane-
embedded receptors, which transduce extracellular stimuli into cytoplasmic responses through
long-range allosteric communication. G protein-coupled receptors (GPCRs) constitute the
largest family among these receptors. They are encoded by more than eight hundred genes in
humans and are involved in a large diversity of critical functions but also diseases, making
GPCRs the target of more than 40 % of current marketed drugs. Although a wealth of genomic
and functional data is available on these receptors, the lack of high-resolution structural and
mechanistic information hinders the development of specific therapies to modulate their
function. The long-term goal of the proposed research is to develop novel integrated
computational-experimental approaches and use these methods to uncover the sequence,
structure and energetic relationships that govern GPCR interactions with extracellular ligands,
intracellular proteins and GPCR signaling functions. We will address this problem using
structure modeling, computational protein design, statistical analysis and experimental
approaches. Specifically, we will develop novel computational techniques to model how a large
diversity of regulatory molecules (ranging from solvent to lipids and peptides) binds to GPCRs
even when no structural information is available on the molecules. We will also combine
computational design and experimental approaches to uncover the allosteric determinants
underlying GPCR signal transductions and use this knowledge to design GPCRs with
reprogrammed signaling activities. Lastly, we will engineer novel GPCR/G protein signaling
pairs to study the binding specificity determinants between receptors and effectors and to
generate signaling switches that may prove useful for improving immune cell engineering in
future immunotherapeutic applications. These studies, by advancing capabilities for predicting
GPCR structures and their interactions with a wide diversity of molecules and for designing
receptors modulating intracellular signaling pathways, will have high biomedical significance.

## Key facts

- **NIH application ID:** 9990830
- **Project number:** 5R01GM097207-09
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Patrick Daniel Barth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $327,684
- **Award type:** 5
- **Project period:** 2012-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990830

## Citation

> US National Institutes of Health, RePORTER application 9990830, EXPLORING STRUCTURE AND SEQUENCE SPACES OF G PROTEIN-COUPLED RECEPTOR SIGNALING (5R01GM097207-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9990830. Licensed CC0.

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