# A New Pradigm for the Rational Expression of Integral Membrane Proteins

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2020 · $369,690

## Abstract

ABSTRACT
Integral membrane proteins (IMPs) are of both fundamental scientific and medical importance, because they govern the
flow of nutrients and information across cell membranes and because they comprise the largest class of therapeutic drug
targets. However, the structural and biophysical characterization of IMPs lags far behind that of other protein classes, due
to the inability to reliably produce significant quantities of IMPs for experimental studies. The fundamental gap in
knowledge is that no framework currently exists for understanding the connection between the amino-acid and nucleotide
sequence of an IMP and its expression level, and the fundamental gap in technology is that
no successful strategies exist
for the general prediction and improvement IMP expression levels.
The current work will remove these fundamental gaps
in knowledge and technology via the innovative combination of (i) experimental methods to characterize IMP expression
levels, spanning across multiple protein families and expression systems, (ii) rigorous data-driven strategies to disentangle
the role of diverse IMP sequence properties on expression, and (iii) coarse-grained molecular dynamics methods to enable
the simulation - on unbiased biological timescales - of key mechanistic steps that act as bottlenecks to IMP expression.
The proposed collaboration of the Miller and Clemons laboratories at Caltech is uniquely positioned to succeed in this
effort, creating the opportunity for a new paradigm for the rational expression of IMPs. Success of the proposed research
will have transformational impact by providing powerful and accessible computational tools for increased IMP expression
to the research community, by advancing the fundamental characterization of this large and important class of proteins,
and by accelerating medical and pharmaceutical applications.

## Key facts

- **NIH application ID:** 9986784
- **Project number:** 5R01GM125063-04
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** William M. Clemons
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $369,690
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986784

## Citation

> US National Institutes of Health, RePORTER application 9986784, A New Pradigm for the Rational Expression of Integral Membrane Proteins (5R01GM125063-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9986784. Licensed CC0.

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