# Computational Exploration of Plant Natural Products Bioactivity and Bioavailability in Human Health

> **NIH NIH R35** · MICHIGAN STATE UNIVERSITY · 2024 · $375,308

## Abstract

Natural products, par�cularly those derived from plants, are some of the most widely used
small-molecule drugs today, with over half of all drugs approved in the past four decades
naturally derived or closely related to natural products. This project uses computa�onal
approaches to model nanoscale interac�ons between natural products from plants, fungi, or
bacteria and their environment to facilitate use and effec�veness for natural products in human
health and disease contexts. To this end, we have developed a molecular simula�on campaign
to quan�fy the ligand-protein and ligand-membrane interac�ons fundamental to natural
product u�liza�on and extrac�on. Since the natural product landscape is so broad, our focus is
directed towards exis�ng compounds where we have exis�ng collabora�ons. For lignin, a
polyaroma�c polymer found in plant cell walls, we are measuring binding to human hormone
receptors to evaluate its poten�al as a replacement plas�cizer in industrial applica�ons.
Cisprenyltransferase and the long polyisoprenoid chains it synthesizes offer a unique look at
how natural product synthesis is controlled, even if the ligand does not fit inside the protein
ac�ve site. Similarly, iden�fying a mitochondrial target for sorgoleone, a compound excreted in
large quan��es by sorghum roots, would open new avenues to probe and alter metabolism in
mitochondria. Other calcula�ons explore the membrane permeability of specific natural
products used to treat cancer, such as vinblas�ne or taxol, across mul�ple membrane
composi�ons to elucidate if membrane permeability changes between cell types drive
differen�al efficacy of cancer treatments. A further systema�c treatment of membrane
permeability in mul�component membrane models could pave the way for connec�ng modern
lipidomics and transport kine�cs for small molecules. The simula�ons involved in this research
use advanced sampling techniques like Hamiltonian replica exchange umbrella sampling (REUS),
or free energy perturba�on (FEP) already used extensively in the PI laboratory to measure
quan��es such as binding affini�es, free energy profiles across biological membranes, and other
measures cri�cal to the biophysics of natural products in vivo.

## Key facts

- **NIH application ID:** 10938269
- **Project number:** 1R35GM155317-01
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Joshua V. Vermaas
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $375,308
- **Award type:** 1
- **Project period:** 2024-06-10 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10938269

## Citation

> US National Institutes of Health, RePORTER application 10938269, Computational Exploration of Plant Natural Products Bioactivity and Bioavailability in Human Health (1R35GM155317-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10938269. Licensed CC0.

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