Navigation Links
Speed plays crucial role in breaking protein's H-bonds
Date:10/30/2007

Researchers at MIT studying the architecture of proteins have finally explained why computer models of proteins behavior under mechanical duress differ dramatically from experimental observations. This work could have vast implications in bioengineering and medical research by advancing our understanding of the relationship between structure and function in these basic building blocks of life.

In a paper published as the cover article of the Oct. 16 issue of the Proceedings of the National Academies of Science (PNAS), the scientists, who work with atomistic modelsaccurate representations of nature that use fundamental laws of atomistic interactions as their basisshow for the first time the basic rupture mechanisms of protein structures when protein strands unfold in response to pressure.

We have for the first time simulated the behavior of protein structures under conditions that correspond to those in living biological systems, said Markus Buehler, the Esther and Harold E. Edgerton Assistant Professor in MITs Department of Civil and Environmental Engineering and lead researcher on the team. All the different types of proteins we studied exhibit two distinct fracture modes that are dependent on the speed at which force is applied. Now we understand that what seemed unrealistic in the earlier computer simulations was actually a consequence of deformation rates and a change in the way hydrogen bonds respond to pressure.

Researchers had puzzled over the vast difference in the amount of pressure required to unfold proteins in experimental versus computer simulation. Earlier computer models forced researchers to apply force at much faster speeds than are possible in the laboratory. As a result, these earlier models predicted that the hydrogen bonds would rupture in response to pressures so small that proteins would be unstable. This clearly isnt the case. Rather, proteins form the structural basis of most biological materials.

It wasnt until the team, using large-scale computing facilities, was able to slow down the application of pressure in their models by a factor of 10 or 20, that they understood the discrepancy. At those speeds, which are much closer to the speeds at which pressure is applied in living cells and tissues, their study showed a change in behavior of the hydrogen bonds.

EXPLAINING THE PUZZLING BEHAVIOR

Buehler and undergraduate student Xuefeng Chen, graduate student Sinan Keten, and Theodor Ackbarow, a graduate student from the University of Stuttgart working in Buehlers lab at MIT, set up a six-month computer simulation study. They worked with two different types of common proteins: vimentinan alpha-helical filament protein that plays an important role in cellular signaling and stabilityand amyloidal fibrilsbeta-folded proteins. These protein motifs form the basis of many natural materials, such as hair, hoof, wool, spider silk, and the prions that build up in the brains of Alzheimers patients.

Hydrogen bonds are the basic chemical bonds that hold together proteins, similar to trusses and beams in buildings, and play a key role in controlling the behavior of these structures.

The researchers placed strain on the proteins by pulling on the ends, trying different pressures applied at different rates. They found that the hydrogen bonds in both the alpha-helical-type vimentin proteins and the beta-fibril-type amyloids behaved similarly. At higher rates, hydrogen bonds begun to break apart one at a time, earlier in the process. But when the pressure is applied more slowly, the bonds hold out longer, but break three at a time when they go.

The slow deformation rate in proteins is most relevant in normal biological function, but the fast rate could be important during tissue injuries such as the shock impact in accidents and during formation of fractures in biological tissues, said Buehler.

This work adds an important piece of knowledge to engineers understanding of how organic materials work efficiently and provides important insight into how a proteins structure defines its unique mechanical properties. They showed that in order to enhance a proteins mechanical strength, the strands of amino acids should fold so that three or four parallel hydrogen bonds form at each convolution of the protein. Experimental evidence shows that proteins actually do fold so that hydrogen bonds form at the rate of 3.6 bonds per convolution.

In addition to enhanced strength, the proteins geometry also leads to a highly robust structure that provides it with an 80 percent robustness rate, giving it very high marks from an engineering perspective. (A 100 percent rating could be applied only to a fail-safe structure.) This 80 percent level of robustness, while simultaneously providing significant mechanical strength enables the biological structure to minimize the use of materials and make it efficient overall and able to sustain extreme mechanical conditions, said the authors.

By contrast, the lack of robustness in many synthetic materials makes it necessary for engineers to introduce large safety factors that guarantee a structures functionality under extreme conditions. For instance, an engineering structure such as a tall building must be able to withstand loads that are 10 times greater than usual, just to protect it in case of one tiny crack, said Buehler. By studying biological building materials and using a bottom-up structural design and synthesis approach, we hope to discover new ways to create stronger synthetic materials, he said.

This new understanding could lead to the development of stronger, more robust materials that consume less energy in their manufacturing and transport. Such advances are only possible by including the molecular scale into the engineering design approach, said Buehler.


'/>"/>
Contact: Denise Brehm
brehm@mit.edu
617-253-8069
Massachusetts Institute of Technology, Department of Civil and Environmental Engineering
Source:Eurekalert

Related biology news :

1. First atlas of key brain genes could speed research on cancer, neurological diseases
2. Influenza vaccine uses insect cells to speed development
3. NIH Calls on Scientists to Speed Public Release of Research Publications
4. Computational Method Speeds Mapping of Cell Signaling Networks
5. FDA Works To Speed The Advent Of New, More Effective Personalized Medicines
6. Rabies spread speeds up
7. New technique may speed DNA analysis
8. Scientists discover gene that controls speed of tuberculosis development
9. Flies on speed offer insight into the roles of dopamine in sleep and arousal
10. Stressed cells spark DNA repair missteps and speed evolution
11. UW scientists report a new method to speed bird flu vaccine production
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/13/2016)... April 13, 2016  IMPOWER physicians supporting Medicaid patients ... a new clinical standard in telehealth thanks to a ... the higi platform, IMPOWER patients can routinely track key ... body mass index, and, when they opt in, share ... visit to a local retail location at no cost. ...
(Date:3/31/2016)... -- Genomics firm Nabsys has completed a financial  restructuring under ... M.D., who returned to the company in October 2015. ... including Chief Technology Officer, John Oliver , Ph.D., ... Vice President of Software and Informatics, Michael Kaiser ... Bready served as CEO of Nabsys from 2005-2014 and ...
(Date:3/23/2016)... , March 23, 2016 ... Interesse erhöhter Sicherheit Gesichts- und Stimmerkennung mit ... Inc. (NASDAQ: MESG ), ein ... dass das Unternehmen mit SpeechPro zusammenarbeitet, um ... der Finanzdienstleistungsbranche, wird die Möglichkeit angeboten, im ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 2016 /PRNewswire/ - FACIT has announced the creation ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" or "the ... a portfolio of first-in-class WDR5 inhibitors for the ... WDR5 represent an exciting class of therapies, possessing ... for cancer patients. Substantial advances have been achieved ...
(Date:6/23/2016)... , June, 23, 2016  The Biodesign Challenge (BDC), ... new ways to harness living systems and biotechnology, announced ... (MoMA) in New York City . ... participating students, showcased projects at MoMA,s Celeste Bartos Theater ... Antonelli , MoMA,s senior curator of architecture and design, ...
(Date:6/23/2016)... 2016 Apellis Pharmaceuticals, Inc. today announced ... of its complement C3 inhibitor, APL-2. The trials ... dose studies designed to assess the safety, tolerability, ... in healthy adult volunteers. Forty subjects ... single dose (ranging from 45 to 1,440mg) or ...
(Date:6/23/2016)... (PRWEB) , ... June 23, 2016 , ... ... on quality, regulatory and technical consulting, provides a free webinar on ... on July 13, 2016 at 12pm CT at no charge. , Incomplete investigations ...
Breaking Biology Technology: