Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Building a Better Protein

25.02.2009
Rensselaer researchers use computers to find keys to stabilizing proteins

Proteins are widely viewed as a promising alternative to synthetic chemicals in everything from medications to hand lotion.

The naturally occurring molecules have been shown to be more efficient and effective than many of the most sophisticated chemical compounds on the market. But outside the controlled confines of the lab bench, proteins quickly change structure, causing irreversible damage to their functionality and often safety.

Scientists are now searching for ways to increase the stability of proteins. In new research published Feb. 5 in the online Early Edition of the Proceedings of the National Academy of Sciences (PNAS), Rensselaer Senior Constellation Professor George Makhatadze and his colleagues detail a targeted strategy to substantially increase the thermodynamic stability of nearly any protein, while preserving its unique function. Their redesign technique creates proteins that remain stable at temperatures 10 degrees Celsius higher than normal.

To achieve these results, the researchers used high-powered computers to create new and improved versions of two human enzymes. The enzymes are specific types of protein. The two enzymes in the study vary widely in size and functionality, yet both showed substantial increases in stability without loss of function in the body. This supports the idea that the stability of many other proteins could also be greatly stabilized, according to Makhatadze. The researchers are now looking to use the technique to improve that stability of specific proteins with strong industrial and drug development applications.

They developed a computational approach that altered the proteins’ structure and tested it for increased stability. “Our experimental validation of computational results is actually motivated by Thomas Edison, who wrote, ‘Until man duplicates a blade of grass, nature will laugh at his so-called scientific knowledge,’” Makhatadze said.

“There are several viable approaches to optimize proteins,” Makhatadze added. “Many researchers seek to optimize the protein by changing all types of physical interactions within the computer model at once. Instead, we felt that if we could understand one interaction, we could then use it to our advantage to build on the algorithm and then experimentally prove that that property really exists in the real protein system.”

The interaction the researchers focused on was the surface charge of the protein. The investigation of the importance of protein surface structure is a growing area of research within the field. In fact, a 2006 paper in the journal Biochemistry, published by Makhatadze supporting the importance of protein surface structure on stability, was the one of the top five most cited and downloaded papers from the journal that year.

In addition to important potential industrial applications, Makhatadze also believes the research sheds some light on the evolution of proteins. The researchers compared the mutations that they made within the proteins in order to optimize the protein’s performance with the mutations naturally occurring in the proteins from the evolutionary distant organisms. Instead of seeing more mutations along with increased performance as with most evolutionary adaptations, the researchers saw that less frequent mutations resulted in a more stable protein. “This suggests that the stability of proteins might not be evolutionarily important,” he said. “It appears that as soon as the protein is able to function in given conditions and is stable at a given temperature, anything above that is not really necessary.”

The research was fully funded by the National Science Foundation (NSF). Makhatadze was assisted in his research by post-doctoral researcher Mayank Patel, graduate student Jiajing Liu, NMR Core Director Scott McCallum, and Assistant Professor of Biology Chunyu Wang, all of Rensselaer, as well as former graduate student Alexey Gribenko, who is currently a member of the faculty at the University of Texas Medical Branch. In addition, the structure of one the proteins used in the study, acylphosphatase (AcPh), was actually solved at Rensselaer using the sophisticated nuclear magnetic resonance (NMR) core within the Center for Biotechnology and Interdisciplinary Studies (CBIS).

Gabrielle DeMarco | EurekAlert!
Further information:
http://ww.rpi.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 >>>