# Toolkit for High-Resolution Structure and Dynamics of Functional Lipids

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $955,103

## Abstract

Project Summary
Membrane proteins are abundant in eukaryotic cells and play important roles in a great many biological
processes ranging from cell adhesion and recognition to energy production to signaling cascades.
Furthermore, membrane proteins make up about 60% of the targets for currently approved drugs, which
underscores their relevance to human disease. Although very high resolution structures of a number of
membrane proteins have now been solved, we lack methods that will also allow us to resolve the structures of
the membrane lipids that interact with membrane-embedded proteins, peripheral membrane proteins and other
ligands. This is in spite of the fact that specific membrane lipids play key regulatory roles in biology. We term
these “functional lipids” because, in addition to their well-known structural roles in membranes, it is becoming
increasingly clear that lipids are effector molecules that modulate and/or directly carry out essential biological
functions. An atomic-scale understanding of the interactions carried out by functional lipids is an important
unmet goal with direct relevance to human health and disease. Thus, although excellent methods now exist for
solving the structures of proteins—including membrane proteins—at very high resolution, the field lacks tools
necessary to solve the structures of the lipid part of membranes at high resolution. This ambitious project aims
to develop an innovative “toolkit” of high-resolution methods for the scientific community to use in solving the
structures of lipids that regulate the biological functions of membranes. Our approach requires synergistic and
coordinated efforts throughout: (1) cost-effective, site-specific isotopic labeling of a variety of phospholipids and
sterols; (2) assembling labeled lipids into nanoscale lipid bilayer systems together with their biologically
relevant ligands; (3) nuclear magnetic resonance (NMR) approaches, principally high-field magic-angle
spinning solid-state NMR (SSNMR), to obtain detailed structural information about the lipids interacting with
ligands; (4) cutting-edge computational methods employing molecular dynamics (MD) simulations of lipids
interacting with ligands in bilayers or bilayer mimetics; and (5) new methods for solving lipid structures by
marrying computational NMR and MD approaches to address the unique challenges inherent in interpreting
and understanding spectral data obtained from planar bilayers that contain repeating copies of labeled lipids
interacting with neighboring lipids in addition to their specific ligands. As our studies progress, we propose to
apply this toolkit to exemplary problems in biology, including blood coagulation, antimicrobial peptide action
and sterol recognition.

## Key facts

- **NIH application ID:** 9985903
- **Project number:** 5R01GM123455-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** James H. Morrissey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $955,103
- **Award type:** 5
- **Project period:** 2016-09-13 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985903

## Citation

> US National Institutes of Health, RePORTER application 9985903, Toolkit for High-Resolution Structure and Dynamics of Functional Lipids (5R01GM123455-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9985903. Licensed CC0.

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