# Molecular Details of Psychoactive Drug Actions

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $629,016

## Abstract

PROJECT SUMMARY:
Scientific summary:
The 5-HT2-serotonin family of receptors represents essential drug targets for most atypical
antipsychotics as well as drugs useful in treating obesity, sleep disorders, psychosis and autistic-
spectrum disorders. It is currently unknown how these drugs interact with their target receptors. Here
we aim to obtain high resolution structures of 5-HT2-family receptors bound to various transducers (G
proteins and arrestins) and biased and unbiased agonists. We will use these structures to prosecute
ultra-large-scale docking campaigns (up to 15 billion novel compounds) to discover improved chemical
tools for these receptors.
These studies are both innovative technically and conceptually by providing an unprecedented
understanding of the molecular and atomic details responsible for psychoactive drug actions.
Additionally, models which attempt to explain ligand-specific properties of biased signaling from the
perspective of ligand-receptor interactions will be tested by a combination of direct structural studies,
molecular modeling, docking, site-directed mutagenesis and functional studies. We anticipate that
our studies will reveal key ligand-receptor interactions essential for biased signaling for serotonin
receptors. Elucidating the molecular details for such interactions provides a
template for the structure-guided design of novel therapeutics.

## Key facts

- **NIH application ID:** 10366918
- **Project number:** 2R01MH112205-06
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Bryan L. Roth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $629,016
- **Award type:** 2
- **Project period:** 2017-03-06 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10366918

## Citation

> US National Institutes of Health, RePORTER application 10366918, Molecular Details of Psychoactive Drug Actions (2R01MH112205-06). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10366918. Licensed CC0.

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