Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Beyond biology: Simple system yields custom-designed proteins

31.10.2003


Technique could lead to new drugs as well as industrial processes



The diversity of nature may be enormous, but for Michael Hecht it is just a starting point.

Hecht, a Princeton professor of chemistry, has invented a technique for making protein molecules from scratch, a long-sought advance that will allow scientists to design the most basic building blocks of all living things with a variety of shapes and compositions far greater than those available in nature.


The technique, which Hecht developed over the last 10 years and validated in experiments to be published in November, could prove useful in a wide range of fields. Custom-designed proteins, for example, could become a source of new drugs or could form the basis of new materials that mimic the strength and resilience of natural substances.

The range of proteins present in nature, while great, has evolved only as far as the needs of biological organisms, said Hecht. "Why should we be limited by a mere few million proteins?" he said. "We can now not only ask what already exists in the biological world, but go beyond that and ask what might be possible."

Hecht and colleagues from Princeton and Rutgers University reported the advance in a paper to be published Nov. 11 in the Proceedings of the National Academy of Sciences. Co-authors of the article are former Princeton graduate student Yinan Wei and Rutgers chemistry professor Jean Baum and her colleagues Seho Kim and David Fela.

Nearly all the internal workings of living things are built from proteins. While genes are the "blueprints" for organisms, proteins are the products built from those instructions. The molecules that transmit signals in the brain, carry oxygen in the blood and turn genes on and off are all proteins.

Scientists have long wanted to design their own proteins, but doing so has proved a major challenge. Proteins are strings of chemical units called amino acids and are often more than 100 amino acids long. When cells make them, these long chains fold spontaneously into complex three-dimensional shapes that fit like puzzle pieces with other molecules and give proteins their unique abilities. There are 20 different amino acids, so the number of possible combinations is enormous. However, the vast majority of these combinations are useless because they cannot fold into protein-like structures.

The advance reported by Hecht and colleagues involves a simple system for designing amino acid sequences that fold like natural proteins. First publishing the idea in 1993, Hecht realized that some amino acids were strongly "water-loving" while others were "oil-loving." The two types naturally separate from each other, with the oil-loving ones clustering in the protein core and water-loving ones forming the perimeter. He also saw that natural proteins with good structures tend to have certain repeating patterns of oil-loving and water-loving amino acids. For example, taking a string of water-loving units -- no matter which ones -- and inserting any oil-loving unit every three or four positions typically creates proteins that fold into bundles of helices.

Hecht used this method to create a "library" of genes encoding millions of novel proteins, each designed to fold into a bundle of four helices. Initial tests of the library in the early 1990s showed that most of the proteins folded into compact arrangements, but these were "mushy," fluctuating shapes instead of well-ordered, rigid structures.

Hecht suspected that these proteins were simply too short to achieve a good structure and added amino acids to each sequence, making them 40 percent longer. In their latest findings, the researchers found that this new library contained well-folded proteins. They subjected one to a painstaking test -- a type of MRI for molecules -- and verified its three-dimensional structure. The experimentally determined structure closely matches that expected from the design.

The results are "quite important work," according to Jane Richardson, a biochemist at Duke University, and are a "direct demonstration of the importance of one simple and central factor in protein folding, which has not in the past been much emphasized in either the design or the folding fields."

Previously, the only ways for scientists to invent new proteins have been to churn out random sequences and screen them for well-folded proteins or to calculate, atom-by-atom, combinations that will fold into a desired shape. The first is difficult because there are too many combinations to try them all, said Hecht. Making every possible sequence of 100 amino acids would require more than all the atoms in universe, he said. The second, the calculation method, yields only one protein at a time.

Hecht’s method offers a middle ground because it limits the number of possible sequences to those that fit the correct oil-loving/water-loving patterns.

Having a rich variety of custom proteins may allow scientists to consider using them for tasks that do not exist in nature, such as catalyzing industrial chemical reactions, Hecht said. "Critters in nature haven’t been challenged to solve the technological problems we’re faced with today," he said. "If we are limited by what nature has given us, we are not going to tackle those problems."


Additional Contact: Joe Blumberg, Rutgers University,
732-932-7084 x652,
blumberg@ur.rutgers.edu

Steven Schultz | EurekAlert!
Further information:
http://www.princeton.edu/

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>