Featured Research

from universities, journals, and other organizations

Design of self-assembling protein nanomachines starts to click: A nanocage builds itself from engineered components

Date:
June 5, 2014
Source:
University of Washington
Summary:
Biological systems produce an incredible array of self-assembling protein tools on a nanoscale, such as molecular motors, delivery capsules and injection devices. Inspired by sophisticated molecular machines naturally found in living things, scientists want to build their own with forms and functions customized to tackle modern day challenges. A new computational method, proven to accurately design protein nanomaterials that arrange themselves into a symmetrical, cage-like structure, may be an important step toward that goal.

This is a computational model of a successfully designed two-component protein nanocage with tetrahedral symmetry.
Credit: Dr. Vikram Mulligan

A route for constructing protein nanomachines engineered for specific applications may be closer to reality.

Biological systems produce an incredible array of self-assembling, functional protein tools. Some examples of these nanoscale protein materials are scaffolds to anchor cellular activities, molecular motors to drive physiological events, and capsules for delivering viruses into host cells.

Scientists inspired by these sophisticated molecular machines want to build their own, with forms and functions customized to tackle modern-day challenges.

The ability to design new protein nanostructures could have useful implications in targeted delivery of drugs, in vaccine development and in plasmonics -- manipulating electromagnetic signals to guide light diffraction for information technologies, energy production or other uses.

A recently developed computational method may be an important step toward that goal. The project was led by the University of Washington's Neil King, translational investigator; Jacob Bale, graduate student in Molecular and Cellular Biology; and William Sheffler in David Baker's laboratory at the University of Washington Institute for Protein Design, in collaboration with colleagues at UCLA and Janelia Farm.

The work is based in the Rosetta macromolecular modeling package developed by Baker and his colleagues. The program was originally created to predict natural protein structures from amino acid sequences. Researchers in the Baker lab and around the world are increasingly using Rosetta to design new protein structures and sequences aimed at solving real-world problems.

"Proteins are amazing structures that can do remarkable things," King said, "they can respond to changes in their environment. Exposure to a particular metabolite or a rise in temperature, for example, can trigger an alteration in a particular protein's shape and function." People often call proteins the building blocks of life.

"But unlike, say, a PVC pipe," King said, "they are not simply construction material." They are also construction (and demolition) workers -- speeding up chemical reactions, breaking down food, carrying messages, interacting with each other, and performing countless other duties vital to life.

Reporting in the June 5 issue of Nature, the researchers describe the development and application of new Rosetta software enabling the design of novel protein nanomaterials composed of multiple copies of distinct protein subunits, which arrange themselves into higher order, symmetrical architectures.

With the new software the scientists were able to create five novel, 24-subunit cage-like protein nanomaterials. Importantly, the actual structures, the researchers observed, were in very close agreement with their computer modeling.

Their method depends on encoding pairs of protein amino acid sequences with the information needed to direct molecular assembly through protein-protein interfaces. The interfaces not only provide the energetic forces that drive the assembly process, they also precisely orient the pairs of protein building blocks with the geometry required to yield the desired cage-like symmetric architectures.

Creating this cage-shaped protein, the scientists said, may be a first step towards building nano-scale containers. King said he looks forward to a time when cancer-drug molecules will be packaged inside of designed nanocages and delivered directly to tumor cells, sparing healthy cells.

"The problem today with cancer chemotherapy is that it hits every cell and makes the patient feel sick," King said. Packaging the drugs inside customized nanovehicles with parking options restricted to cancer sites might circumvent the side effects.

The scientists note that combining just two types of symmetry elements, as in this study, can in theory give rise to a range of symmetrical shapes, such as cubic point groups, helices, layers, and crystals.

King explained that the immune system responds to repetitive, symmetric patterns, such as those on the surface of a virus or disease bacteria. Building nano-decoys may be a way train the immune system to attack certain types of pathogens.

"This concept may become the foundation for vaccines based on engineered nanomaterials," King said. Further down the road, he and Bale anticipate that these design methods might also be useful for developing new clean energy technologies.

The scientists added in their report, "The precise control over interface geometry offered by our method enables the design of two-component protein nanomaterials with diverse nanoscale features, such as surfaces, pores, and internal volumes, with high accuracy."

They went on to say that the combinations possible with two-component materials greatly expand the number and variety of potential nanomaterials that could be designed.

It may be possible to produce nanomaterials in a variety of sizes, shapes and arrangements, and also move on to construct increasingly more complex materials from more than two components.

The researchers emphasized that the long-term goal of such structures is not to be static. The hope is that they will mimic or go beyond the dynamic performance of naturally occurring protein assemblies, and that eventually novel molecular protein machines could be manufactured with programmable functions.

The researchers pointed out that although designing proteins and protein-based nanomaterials is very challenging due to the relative complexity of protein structures and interactions, there are now more than a handful of laboratories around the world making major strides in this field. Each of the leading contributors have key strengths, they said. The strengths of the UW team is in the accuracy of the match of the designed proteins to the computational models and the predictability of the results.


Story Source:

The above story is based on materials provided by University of Washington. Note: Materials may be edited for content and length.


Journal Reference:

  1. Neil P. King, Jacob B. Bale, William Sheffler, Dan E. McNamara, Shane Gonen, Tamir Gonen, Todd O. Yeates, David Baker. Accurate design of co-assembling multi-component protein nanomaterials. Nature, 2014; 510 (7503): 103 DOI: 10.1038/nature13404

Cite This Page:

University of Washington. "Design of self-assembling protein nanomachines starts to click: A nanocage builds itself from engineered components." ScienceDaily. ScienceDaily, 5 June 2014. <www.sciencedaily.com/releases/2014/06/140605093315.htm>.
University of Washington. (2014, June 5). Design of self-assembling protein nanomachines starts to click: A nanocage builds itself from engineered components. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2014/06/140605093315.htm
University of Washington. "Design of self-assembling protein nanomachines starts to click: A nanocage builds itself from engineered components." ScienceDaily. www.sciencedaily.com/releases/2014/06/140605093315.htm (accessed October 23, 2014).

Share This



More Matter & Energy News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

3D Printed Instruments Make Sweet Music in Sweden

3D Printed Instruments Make Sweet Music in Sweden

Reuters - Innovations Video Online (Oct. 23, 2014) — Students from Lund University's Malmo Academy of Music are believed to be the world's first band to all use 3D printed instruments. The guitar, bass guitar, keyboard and drums were built by Olaf Diegel, professor of product development, who says 3D printing allows musicians to design an instrument to their exact specifications. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Chameleon Camouflage to Give Tanks Cloaking Capabilities

Chameleon Camouflage to Give Tanks Cloaking Capabilities

Reuters - Innovations Video Online (Oct. 22, 2014) — Inspired by the way a chameleon changes its colour to disguise itself; scientists in Poland want to replace traditional camouflage paint with thousands of electrochromic plates that will continuously change colour to blend with its surroundings. The first PL-01 concept tank prototype will be tested within a few years, with scientists predicting that a similar technology could even be woven into the fabric of a soldiers' clothing making them virtually invisible to the naked eye. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Jet Sales Lift Boeing Profit 18 Pct.

Jet Sales Lift Boeing Profit 18 Pct.

Reuters - Business Video Online (Oct. 22, 2014) — Strong jet demand has pushed Boeing to raise its profit forecast for the third time, but analysts were disappointed by its small cash flow. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Internet of Things Aims to Smarten Your Life

Internet of Things Aims to Smarten Your Life

AP (Oct. 22, 2014) — As more and more Bluetooth-enabled devices are reaching consumers, developers are busy connecting them together as part of the Internet of Things. (Oct. 22) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Space & Time

Matter & Energy

Computers & Math

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins