Nav: Home

Protein engineered to detect nerve gas

June 03, 2004

DURHAM, N.C. -- Duke University Medical Center biochemists have used computational design to engineer and construct a protein that could sense the nerve agent soman. They said their achievement constitutes a proof-of principle that such engineered proteins can be made to detect nerve agents such as sarin and other toxic substances.

Such proteins could be incorporated into detectors, which might resemble smoke detectors and could be widely deployed as early-warning alarms, weapons monitors or in the decontamination process after an attack. The detector could not only warn of the presence of the nerve agent, but act as a continuous monitor of its levels.

Led by Associate Professor of Biochemistry Homme Hellinga, Ph.D., the researchers reported their achievement in a paper published online May 17, 2004 in the Proceedings of the National Academy of Sciences. Besides Hellinga, other co-authors of the PNAS paper were Malin Allert, Shahir Rizk and Loren Looger. Their research is sponsored by the Defense Advanced Research Projects Agency.

In the PNAS paper, Helling and his colleagues described how they had designed a protein that detects a surrogate for soman, called pinacolyl methyl phosphonic acid (PMPA), which has the same basic chemical structure as soman, but is less toxic. Soman is a nerve agent first invented by the Germans before World War II and manufactured in large quantities by the former Soviet Union.

In developing the PMPA detector, the Duke researchers used the same general design technique that they had previously used to tailor proteins to sense glucose, lactate, TNT and the brain chemical serotonin.

They began with proteins, called "periplasmic binding proteins," from the gut bacterium E. coli. These proteins are normally part of the bacterium's chemical-sensing system by which it detects nutrients. Such protein receptors detect their target molecule via an "active site" that has a precise complementary shape and binding properties that fit only that molecule, called a "ligand" -- like a key fitting a lock.

Basically, the computational design process developed in Hellinga's laboratory involves redesigning the normal protein's "lock" to fit a very different molecular key. The computational process narrows down to a manageable few the vast number of possible mutations in the normal protein and their corresponding structures, to fit a particular molecule. Once the designs are narrowed down, the biochemists construct the proteins and test them for selectivity and binding properties.

"We chose PMPA because it is a commercially available surrogate of soman and is a breakdown product of the nerve agent," said Hellinga. "The design technique we used can be readily applied to any nerve agent. Also, the design challenge is quite similar to those we faced in designing proteins to detect TNT and other compounds."

Hellinga and his colleagues designed the PMPA-detecting protein not only to highly selectively bind to PMPA, but also to signal that binding by means of an attached fluorescent molecule. Thus, the protein can be incorporated into a detector that would sense a change in fluorescence of the protein as an indicator of the presence and concentration of the nerve agent.

According to Hellinga, the specificity and affinity of the PMPA detector proteins they created are sufficient for development of first-generation detectors. However, the protein must still be made more robust to function stably over long periods of time. Thus, the researchers are experimenting with corresponding proteins from thermophilic bacteria -- known for the robustness of their proteins -- that live in hot springs. The biochemists are also launching efforts to design proteins to detect other nerve agents, including sarin.

"One particularly important aspect of this computational design technique is that it can be done very rapidly," said Hellinga. "It takes at most a day to calculate a set of candidate structures and perhaps a week to construct them. So, in the event of the deployment of a new chemical threat, it might take in principle only weeks to develop a sensor system for it. We're now working to develop an automated laboratory process into a system to fabricate such proteins."

The researchers are working with Nomadics, Inc. of Stillwater, Okla. To develop sensors based on their advances, and they plan further commercialization of the design and synthesis technologies.
-end-


Duke University Medical Center

Related Proteins Articles:

Designing vaccines from artificial proteins
EPFL scientists have developed a new computational approach to create artificial proteins, which showed promising results in vivo as functional vaccines.
New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.
Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.
Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.
Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.
Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.
Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.
Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.
How proteins become embedded in a cell membrane
Many proteins with important biological functions are embedded in a biomembrane in the cells of humans and other living organisms.
Finding the proteins that unpack DNA
A new method allows researchers to systematically identify specialized proteins called 'nuclesome displacing factors' that unpack DNA inside the nucleus of a cell, making the usually dense DNA more accessible for gene expression and other functions.
More Proteins News and Proteins Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.