A new study combining advanced computational modeling and cutting-edge experiments by molecular biologists at Rice University and Baylor College of Medicine suggests that the most stable parts of a protein are also the parts that fold first.
The findings appear in the Sept. 13 issue of the journal Structure.
Nature refuses to choose between form and function when it comes to protein folding; each protein's function is directly related to its shape, and when proteins misfold – something that's known to occur in a number of diseases like Alzheimer's and Huntington's – they don't function as they should.
In the new study, scientists designed and tested a new computational approach that aimed to study proteins with known shapes in order to ascertain which of their parts were the most stable in the face of chemical and thermal fluctuations.
"We found that the most stable parts of the final, folded protein come together first during the folding," said co-author Pernilla Wittung-Stafshede, associate professor of biochemistry and cell biology and of chemistry. She said the findings could help both scientists who are attempting to design synthetic proteins with a particular shape and scientists who are attempting to associate the shape and function of naturally occurring proteins.
The computational approach tested in the experiment was developed by the research group of co-author Jianpeng Ma, associate professor of bioengineering at Rice and associate professor of biochemistry and molecular biology at Baylor College of Medicine. Ma's group, which mainly focuses on multi-scale protein structure modeling and prediction, developed highly accurate knowledge-based potential functions that made the current collaborative study possible.
"As far as we know, no one has ever used this type of knowledge-based, statistical approach to predict the stability cores of proteins," Ma said. "Our results suggest that thermodynamics and kinetics are closely correlated in proteins and appear to have co-evolved for optimizing both the folding rate and the stability of proteins."
Wittung-Stafshede's group, which specializes in experimental studies related to protein folding, tested the model's predictions against experimental data gathered for several forms of the protein azurin, a copper-containing protein that folds into a sandwich-like structure called a beta sheet, which is a common fold in nature that consists of two beta-sheets of amino-acid strands meshed together.
"In folding study the right combination of expertise in computational and experimental approaches is vital for success," Ma said. "Our collaborative team has set an excellent example for future study."
Jade Boyd | EurekAlert!
New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg
Disarray in the brain
18.12.2017 | Universität zu Lübeck
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
18.01.2018 | Life Sciences
18.01.2018 | Life Sciences
18.01.2018 | Earth Sciences