# Forces Driving Membrane Protein Folds

> **NIH NIH R35** · JOHNS HOPKINS UNIVERSITY · 2024 · $85,682

## Abstract

Project Summary
 Understanding how proteins fold is a central quest in biology. Studied for over 50
years, investigations of soluble protein folding have proven invaluable for dissecting the
molecular basis of a multitude of diseases. By comparison, folding studies of membrane
proteins lag far behind. The knowledge gained from soluble protein studies cannot simply
be transferred to inferences about because their solvents are different. The balance of
forces encoding a MP embedded in a lipid bilayer must be distinct from that of soluble
proteins in water.
 Our research efforts contribute to filling this key gap in the understanding the physical
chemistry of membrane proteins. We will experimentally determine of energetic forces
stabilizing membrane proteins along the steeply changing polarity gradient of the
phospholipid bilayer interface, quantify backbone hydrogen bond strengths, and expand
our repertoire of membrane protein folding models to include those with an a-helical
secondary structure. These efforts will be complemented by molecular simulations and
other solution biophysics interrogations as needed.
 Our results have broad ranging impact in the field at large through contributions to
information databases used in training computational algorithms and by their
incorporation in physically realistic mechanisms for protein folding catalysis by cellular
machines.

## Key facts

- **NIH application ID:** 11036555
- **Project number:** 3R35GM148199-02S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Karen G. Fleming
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $85,682
- **Award type:** 3
- **Project period:** 2023-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11036555

## Citation

> US National Institutes of Health, RePORTER application 11036555, Forces Driving Membrane Protein Folds (3R35GM148199-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11036555. Licensed CC0.

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