Drug Discovery and Development

  • Home Drug Discovery and Development
  • Drug Discovery
  • Women in Pharma and Biotech
  • Oncology
  • Neurological Disease
  • Infectious Disease
  • Resources
    • Video features
    • Podcast
    • Voices
    • Views
    • Webinars
  • Pharma 50
    • 2025 Pharma 50
    • 2024 Pharma 50
    • 2023 Pharma 50
    • 2022 Pharma 50
    • 2021 Pharma 50
  • Advertise
  • SUBSCRIBE

New Method Simplifies the Search For Protein Receptor Complexes, Speeding Drug Development

By University of Wisconsin - Milwaukee | May 20, 2019

Valerica Raicu, professor of physics at the University of Wisconsin-Milwaukee, uses photon excitation spectrography to help characterize protein receptor responses to drug compounds. Credit: Troye Fox

For a drug to intervene in cells or entire organs that are not behaving normally it must first bind to specific protein receptors in the cell membranes. Receptors can change their molecular structure in a multitude of ways during binding – and only the right structure will “unlock” the drug’s therapeutic effect.

Now, a new method of assessing the actions of medicines by matching them to their unique protein receptors has the potential to greatly accelerate drug development and diminish the number of drug trials that fail during clinical trials.

The method, developed by research teams from the University of Wisconsin-Milwaukee and the University of Glasgow, reduces the time and labor of finding the protein receptors “with the right response” to drug candidates by several orders of magnitude.

“It opens up a huge playing field for finding drug targets and drug stratification,” said Valerica Raicu, UW-Milwaukee professor of physics. “Using this method, we can characterize how each receptor responds differently to various drug candidates.”

The study appears today in the journal Nature Methods.

The researchers’ method tracks a chemical process called oligomerization that occurs when a receptor exists as a single subunit, but then shifts to a multi-structure – an oligomer – in the presence of the ligand (drug compound), or vice versa.

“We used to think of these receptors as binary,” said Raicu, who is lead author on the paper. “They were either activated by the compound or not. But now we are beginning to understand that, depending on the ligand, the same receptor can produce many different responses.”

The researchers first tested the method using fused florescent proteins produced by UW-Milwaukee assistant professor Ionel Popa. Then they validated the method on a receptor for a growth factor where malfunction is often linked to cancer – the epidermal growth factor receptor (EGF). Activation of the receptor, resulted in the generation of larger oligomers, as anticipated.

The team then applied their method to a member of the G protein-coupled receptor (GPCR) family, a group of proteins that are targeted by a wide range of medicines.

The effect of the association between ligands and receptors was shown in a matter of hours, compared to months using current technologies.

“This new method of characterizing protein interactions will be important in the stratification of different medicines that target the same receptor,” said Graeme Milligan, Gardiner Chair of Biochemistry at the University of Glasgow. “It will allow us to understand why some drug candidates are effective while others are not and can potentially be applied to different classes of proteins that are targets in the treatment of many diseases.”

The Raicu lab uses fluorescence-based imaging in order to see protein receptors in oligomeric states under various environmental conditions. Using single- or two-photon excitation microscopy, the researchers can produce a kind of roadmap of the various kinds of protein receptor oligomers in the absence or presence of ligands (or drugs) that bind to them.

Researchers image protein-receptor molecules by attaching florescent tags. This way, single-molecule protein receptors give off light when they pass under a laser and are excited, and those bursts are recorded with a camera. Receptor oligomers give off a more intense burst of light and those are also photographed.

“Now you can graph the intensity and the number of bursts,” said Raicu, “and see how many are associated into oligomers – how big they are – and where they are in the sample. After adding the ligand, you can see whether it promotes association of single molecules of receptor proteins into oligomers, or the breakdown of oligomers into the former.”


Filed Under: Drug Discovery and Development

 

Related Articles Read More >

Columbia-CZ team develops 10.3M parameter model that outperforms 100M parameter rivals on cell type classification
Collage of close-up male and female eyes isolated on colored neon backgorund. Multicolored stripes. Concept of equality, unification of all nations, ages and interests. Diversity and human rights
How a ‘rising tide’ of inclusivity is transforming clinical trials
Mary Marcus appointed CEO of NewAge Industries
DNA double helix transforming into bar graphs, blue and gold, crisp focus on each strand, scientific finance theme --ar 5:4 --personalize 3kebfev --v 6.1 Job ID: f40101e1-2e2f-4f40-8d57-2144add82b53
Biotech in 2025: Precision medicine, smarter investments, and more emphasis on RWD in clinical trials
“ddd
EXPAND YOUR KNOWLEDGE AND STAY CONNECTED
Get the latest news and trends happening now in the drug discovery and development industry.

MEDTECH 100 INDEX

Medtech 100 logo
Market Summary > Current Price
The MedTech 100 is a financial index calculated using the BIG100 companies covered in Medical Design and Outsourcing.
Drug Discovery and Development
  • MassDevice
  • DeviceTalks
  • Medtech100 Index
  • Medical Design Sourcing
  • Medical Design & Outsourcing
  • Medical Tubing + Extrusion
  • Subscribe to our E-Newsletter
  • Contact Us
  • About Us
  • R&D World
  • Drug Delivery Business News
  • Pharmaceutical Processing World

Copyright © 2025 WTWH Media LLC. All Rights Reserved. The material on this site may not be reproduced, distributed, transmitted, cached or otherwise used, except with the prior written permission of WTWH Media
Privacy Policy | Advertising | About Us

Search Drug Discovery & Development

  • Home Drug Discovery and Development
  • Drug Discovery
  • Women in Pharma and Biotech
  • Oncology
  • Neurological Disease
  • Infectious Disease
  • Resources
    • Video features
    • Podcast
    • Voices
    • Views
    • Webinars
  • Pharma 50
    • 2025 Pharma 50
    • 2024 Pharma 50
    • 2023 Pharma 50
    • 2022 Pharma 50
    • 2021 Pharma 50
  • Advertise
  • SUBSCRIBE