(Press-News.org) A cheetah lies still in the grass. Finally, a gazelle comes into view. The cheetah plunges forward, reaches sixty-five miles per hour in three seconds, and has the hapless gazelle by the jugular in less than a minute. Then it must catch its breath, resting before eating.
A blue whale surfaces, blasting water high from its blowhole. It breathes in great gasps, filling its thousand-gallon lungs with air. Then it descends again to look for krill, staying below for 10, 20, even 30 minutes before taking another breath.
Both animals need oxygen, of course. And both depend on the protein myoglobin to store and then release that oxygen within their working muscles. But how they need oxygen differs. The whale must have enough to last a whole dive. Its muscles have a high concentration of myoglobin that delivers oxygen steadily. In contrast, the cheetah's myoglobin must perform like a fast-shooting cannon. The cheetah needs to suddenly take up and release large doses of oxygen to stoke its explosive speed.
How does myoglobin do all that? For decades, biologists have wondered how -- and with what atomic motions, exactly -- the folded structure of myoglobin allows it to hold and release oxygen.
Now, two physicists at the University of Vermont have an answer. They've developed a new way to peer into the inner workings of proteins and detect which specific atoms are at work. Their work was published in the Aug. 27 issue of the journal Physical Review Letters.
Using myoglobin as a test, the scientists were able to home in on the critical functional piece of the protein, separating it from the vast number of other "jigglings and wigglings of atoms" says William DeWitt, a UVM graduate student and the lead author on the paper that describes the finding.
"We've been able to identify the motion of one particular amino acid -- this group of atoms called the distal histidine -- that controls the binding process," he says.
Shaped a bit like a tennis racket over a basket, this tiny arm of the protein moves, through thermal fluctuations, to open or close the binding site near the myoglobin's iron-filled center. "As the atoms move in one direction it becomes easier to bind oxygen," says DeWitt, "and as they move in the reverse direction it becomes less easy."
And how this distal histidine moves should vary between the whale and the cheetah. "I would imagine," says Kelvin Chu, associate professor of physics and DeWitt's co-author, "that there has been evolutionary pressure on every species to adapt this motion in the myoglobin for their particular oxygen-binding needs."
"That's a testable hypothesis," Chu says. "What we would expect to see across species is that the tennis rackets are in different places or move different amounts."
DeWitt and Chu's work extends far beyond myoglobin. The two physicists see broad application of their new method in creating custom-crafted proteins.
"Once you know what these motions are and what the important atoms are," says Chu, "you can make mutants of proteins that have different binding attributes." And these different attributes have promise in developing new biotechnologies "ranging from blood substitutes to organic solar cells," he says.
Proteins are a cell's heavy laborers: hauling water, taking out the trash, carrying in the groceries -- and trillions of other tasks that make life. But how the shape of a protein determines its function remains one of the most vexing and important questions in the physics of biology.
Proteins are not the static, Lego-like objects you might see in an x-ray photograph in a biochemistry textbook. Instead, made from long chains of amino acids scrunched into various blobs and globs, a protein is always jumping between slightly different structural arrangements due to thermal motion of its atoms. Even a modest-sized protein like myoglobin has more possible arrangements of its atoms than there are stars in the universe. And each of these arrangements slightly changes a protein's function.
"But what are the important motions that control its function?" asks Chu.
"Relating the structure of a protein to what it is doing is the holy grail," he says. For myoglobin at least, the two UVM scientists seem to have brought the prize a lot closer to hand.
Their method -- called temperature derivative spectroscopy or TDS -- involves cooling myoglobin to as low as -450 degrees Fahrenheit, about 18 degrees above absolute zero, and then measuring its oxygen-binding process. At these chilly temperatures, each protein basically gets stuck in just one arrangement. These individual atomic arrangements can't be observed directly, but, using infrared light, a pack of myoglobin molecules does yield a kind of group portrait -- a summing, called a TDS surface -- of the position of all the proteins as they bind to the oxygen in carbon monoxide.
The Vermont scientists' innovation comes largely from what they have been able to do with this group portrait.
"This scenario is called an inverse problem," DeWitt notes, "we have measured the effect but want to determine the cause." Unfortunately, a bit like asking what two numbers add up to ten, there are many solutions.
But, usually, nature does not build wasteful structures -- and though the universe is undoubtedly complex, it does not seem given to capricious complexity. In other words, the scientific principle of parsimony -- what philosophy students encounter as Occam's Razor -- suggests that the least complex explanation is the most likely.
Applying a mathematical version of this idea from Bayesian statistics, called the principle of maximum entropy, DeWitt and Chu went looking for the simplest solution to the TDS surface created by their group of myoglobin molecules. And the answer: the motion of the distal histidine most simply explains how myoglobin regulates oxygen binding.
They followed this prediction by performing a computer simulation of the molecular dynamics of the distal histidine, which confirmed their interpretation.
"Will did a lot of this on his own," says Chu, "He took the data, and the analysis was done on a MacPro," plus some time on the National Science Foundation's high-performance computer network, the TeraGrid.
"He's a clever guy," says Chu.
INFORMATION:
Slicing proteins with Occam's Razor
Vermont scientists invent new way to view atomic motion of proteins
2010-10-01
ELSE PRESS RELEASES FROM THIS DATE:
Iowa State University researcher examines mosquito gene for new disease response
2010-10-01
Ames, Iowa - An Iowa State University researcher searched for new genes that are turned on during infection in a type of mosquito that is not only a pest, but transmits disease-causing pathogens.
Lyric Bartholomay, assistant professor of entomology, along with colleagues from around the world, infected the common southern house mosquito (Culex quinquefasciatus) with various pathogens to see which mosquito genes are activated in response to the infection.
Bartholomay is the first author on the paper, "Pathogenomics of Culex quinquefasciatus and Meta-Analysis of Infection ...
Short and long sleep in early pregnancy linked to high blood pressure in the third trimester
2010-10-01
DARIEN, IL – A study in the Oct. 1 issue of the journal Sleep found that getting too little or too much sleep in early pregnancy is associated with elevated blood pressure in the third trimester. The study suggests that improving prenatal sleep hygiene may provide important health benefits.
Results show that the mean systolic blood pressure in the third trimester was 114 mm Hg in women with a normal self-reported nightly sleep duration of nine hours in early pregnancy, 118.05 mm Hg in women who reported sleeping six hours or less per night, and 118.90 mm Hg in women ...
Is photoscreening the best way to catch 'lazy eye'?
2010-10-01
SAN FRANCISCO, CA– Amblyopia, known as "lazy eye," is a major cause of vision problems in children and a common cause of blindness in people aged 20 to 70 in developed countries. In amblyopia the person's stronger eye is favored and his/her weaker eye gradually loses visual power as a result. When the condition is detected and treated before age 7, more than 75 percent of children achieve 20/30 vision or better, the Amblyopia Treatment Study reports. But parents and teachers can easily miss this problem–especially in very young children. Pediatric ophthalmologists (Eye ...
Most suicidal adolescents receive follow-up care after ER visits
2010-10-01
SAN FRANCISCO – For suicidal adolescents, the emergency department (ED) is most often the chosen portal to mental health services. New research, presented Friday, Oct. 1, at the American Academy of Pediatrics (AAP) National Conference and Exhibition in San Francisco, looks at what happens to the 30 percent of suicidal adolescents who are discharged from the ED and whether they go on to access additional mental health services.
In "Predictors of Mental Health Follow up Among Adolescents with Suicidal Ideation After Emergency Department Discharge," researchers followed ...
New lung cancer research finds half of advanced lung cancer patients receive chemotherapy
2010-10-01
For the first time to date, research published in the October edition of the Journal of Thoracic Oncology (JTO) sought to determine the use of chemotherapy in a contemporary, diverse non-small cell lung cancer (NSCLC) population encompassing all patient ages. Prior population-based studies have shown that only 20 to 30 percent of advanced lung cancer patients receive chemotherapy treatment. These studies have previously relied on the Medicare-linked Surveillance, Epidemiology, and End Results (SEER) database, thus excluding the 30 to 35 percent of lung cancer patients younger ...
TRUST study data confirms safety and efficacy of erlotinib for advanced lung cancer
2010-10-01
Featured in the October edition of the Journal of Thoracic Oncology (JTO), data from The Tarceva Lung Cancer Survival Treatment (TRUST) confirms the safety and efficacy profile of erlotinib, a highly potent oral active, reversible inhibitor of epidermal growth factor receptor (EGFR) tyrosine-kinase (TK) activity in a large heterogeneous non-small cell lung cancer (NSCLC) population.
Erlotinib has been shown to significantly increase survival for patients with previously treated advanced NSCLC. Certain groups of patients with NSCLC, such as those with a particular type ...
Genetically altered trees, plants could help counter global warming
2010-10-01
Forests of genetically altered trees and other plants could sequester several billion tons of carbon from the atmosphere each year and so help ameliorate global warming, according to estimates published in the October issue of BioScience.
The study, by researchers at Lawrence Berkeley National Laboratory and Oak Ridge National Laboratory, outlines a variety of strategies for augmenting the processes that plants use to sequester carbon dioxide from the air and convert it into long-lived forms of carbon, first in vegetation and ultimately in soil.
Besides increasing the ...
Adjunctive rufinamide reduces refractory partial-onset seizures
2010-10-01
Researchers from the Arkansas Epilepsy Program found treatment with rufinamide results in a significant reduction in seizure frequency compared with placebo, for patients with uncontrolled partial-onset seizures (POS). Details of this study are now available online in Epilepsia, a journal published by Wiley-Blackwell on behalf of the International League Against Epilepsy.
Epilepsy affects up to 2% of the worldwide population according to the Centers for Disease Control and Prevention. More than half of these patients experience POS, or focal seizures, which are initiated ...
Researchers find no difference in drugs for macular degeneration
2010-10-01
(Boston) – Researchers from Boston University School of Medicine (BUSM) and the VA Boston Healthcare System have conducted a study that failed to show a difference in efficacy between Bevacizumab (Avastin) and Ranibizumab (Lucentis) for the treatment of age-related macular degeneration (AMD). The study, which appears currently on-line in Eye, is believed to be the first study to describe one-year outcomes of a prospective, double-masked, randomized clinical trial directly comparing bevacizumab to ranibizuamab. Last October, these same researchers published early, six month ...
Flow of empty calories into children's food supply must be reduced
2010-10-01
St. Louis, MO, October 1, 2010 – With over 23 million children and adolescents in the US overweight or obese, the risks for many chronic diseases continue to increase. An article in the October issue of the Journal of the American Dietetic Association examines the diets of American youth and finds some disturbing results.
"The epidemic of obesity among children and adolescents is now widely regarded as one of the most important public health problems in the US," commented Jill Reedy, PhD, MPH, RD, and Susan M. Krebs-Smith, PhD, MPH, RD, both of the Division of Cancer ...
LAST 30 PRESS RELEASES:
Insulin resistance is linked to over 30 diseases – and to early death in women, study of people in the UK finds
Innovative semaglutide hydrogel could reduce diabetes shots to once a month
Weight loss could reduce the risk of severe infections in people with diabetes, UK research suggests
Long-term exposure to air pollution and a lack of green space increases the risk of hospitalization for respiratory conditions
Better cardiovascular health in early pregnancy may offset high genetic risk
Artificial intelligence method transforms gene mutation prediction in lung cancer: DeepGEM data releases at IASLC 2024 World Conference on Lung Cancer
Antibody–drug conjugate I-DXd shows clinically meaningful response in patients with extensive-stage small cell lung cancer
IASLC Global Survey on biomarker testing reveals progress and persistent barriers in lung cancer biomarker testing
Research shows pathway to developing predictive biomarkers for immune checkpoint inhibitors
Just how dangerous is Great Salt Lake dust? New research looks for clues
Maroulas appointed Associate Vice Chancellor, Director of AI Tennessee
New chickadee research finds cognitive skills impact lifespan
Cognitive behavioral therapy enhances brain circuits to relieve depression
Terasaki Institute awarded $2.3 Million grant from NIH for organ transplantation research using organs-on-a-chip technology
Atoms on the edge
Postdoc takes multipronged approach to muon detection
Mathematical proof: Five satellites needed for precise navigation
Scalable, multi-functional device lays groundwork for advanced quantum applications
Falling for financial scams? It may signal early Alzheimer’s disease
Integrating MRI and OCT for new insights into brain microstructure
Designing a normative neuroimaging library to support diagnosis of traumatic brain injury
Department of Energy announces $68 million in funding for artificial intelligence for scientific research
DOE, ORNL announce opportunity to define future of high-performance computing
Molecular simulations, supercomputing lead to energy-saving biomaterials breakthrough
Low-impact yoga and exercise found to help older women manage urinary incontinence
Genetic studies reveal new insights into cognitive impairment in schizophrenia
Researcher develops technology to provide cleaner energy and cleaner water
Expect the unexpected: nanoscale silver unveils intrinsic self-healing abilities
nTIDE September 2024 Jobs Report: Gains in employment for people with disabilities appear to level off after reducing gaps with non-disabled workers
Wiley enhances NMR Spectral Library Collection with extensive new databases
[Press-News.org] Slicing proteins with Occam's RazorVermont scientists invent new way to view atomic motion of proteins