Duke Research Blog

Following the people and events that make up the research community at Duke.

Category: Chemistry (Page 1 of 5)

Looking at Cooking as a Science Experiment

From five-star restaurants to Grandma’s homemade cookies, cooking is an art that has transformed the way we taste food. But haven’t you ever wondered how cooking works? How in the world did people discover how to make Dipping Dots or Jell-O?

Patrick Charbonneau is an Associate Professor of Chemistry here at Duke and last Friday he gave a delicious talk about the science of cooking (with samples!).

Patrick Charbonneau, Duke Chemist and Foodie

Around 10,000 years ago humans discovered that by fermenting milk you could turn it into yogurt, something that is more transportable, lasts longer, and digests easier. In the 1600s a new cooking apparatus called the “bone digester” (pressure cooker) allowed you to cook things faster while enhancing the flavor. When the 1800s came around, a scientist named Eben Horsford discovered that adding an acid with sodium bicarbonate creates baking powder. Soon enough scientific and kitchen minds started to collaborate, and new creations were made in the culinary world. As you can see, a lot of fundamental cooking techniques and ingredients we use today are a product of scientific discoveries.

Old-school pressure cookers. Forerunners of the Instant Pot.

Whisked Toffee

Freezer toffee, AKA caramel

A huge part of cooking is controlling the transformation of matter, or “a change in phase.” Professor Charbonneau presented a very cool example demonstrating how controlling this phase shift can affect your experience eating something. He made the same toffee recipe twice, but he changed it slightly as the melted toffee mixture was cooling. One version you stick straight in the freezer; the other you whisk as it cools. The whisked version turns out crumbly and sweeter; the other one turns into a chewy, shiny caramel. The audience got samples, and I could easily tell how different each version looked and tasted.

Charbonneau explained that while both toffees have the same ingredients, most people prefer the crumbly one because it seems sweeter (I agreed). This is because the chewier one takes longer to dissolve onto your taste buds, so your brain registers it as less sweet.

I was fascinated to learn that a lot of food is mostly just water. It’s weird to think a solid thing could be made of water, yet some foods are up to 99% water and still elastic! We have polymers — long repeating patterns of atoms in a chain — to thank for that. In fact, you can turn almost any liquid into a gel. Polymers take up little space but play a vital role in not only foods but other everyday objects, like contact lenses.

Charbonneau also showed us a seemingly magical way to make cake. He took about half a Dixie cup of cake batter, stuck a whipping siphon charged with nitrous oxide inside it for a second, then threw it in the microwave for thirty seconds. Boom, easy as cake. Out came a cup full of some pretty darn good fluffy chocolate cake. The gas bubbles in the butter and egg batter expand when they are heated up, causing the batter to gel and form a solid network.

Professor Charbonneau is doing stuff like this in his class here at Duke, “The Chemistry and Physics of Cooking,” all the time.

In the past ten years a surge in science-cooking related classes has emerged. The experiments you could do in a kitchen-lab are so cool and can make science appealing to those who might normally shy away from it.

Another cool thing I learned at the stations outside of Charbonneau’s talk was that Dipping Dots are made by dripping melted ice cream into a bowl of liquid nitrogen. The nitrogen is so cold that it flash-freezes the ice cream droplet into a ball-like shape!

Post by Will Sheehan

Will Sheehan

Stretchable, Twistable Wires for Wearable Electronics

A new conductive “felt” carries electricity even when twisted, bent and stretched. Credit: Matthew Catenacci

The exercise-tracking power of a Fitbit may soon jump from your wrist and into your clothing.

Researchers are seeking to embed electronics such as fitness trackers and health monitors into our shirts, hats, and shoes. But no one wants stiff copper wires or silicon transistors deforming their clothing or poking into their skin.

Scientists in Benjamin Wiley’s lab at Duke have created new conductive “felt” that can be easily patterned onto fabrics to create flexible wires. The felt, composed of silver-coated copper nanowires and silicon rubber, carries electricity even when bent, stretched and twisted, over and over again.

“We wanted to create wiring that is stretchable on the body,” said Matthew Catenacci, a graduate student in Wiley’s group.

The conductive felt is made of stacks of interwoven silver-coated copper nanotubes filled with a stretchable silicone rubber (left). When stretched, felt made from more pliable rubber is more resilient to small tears and holes than felts made of stiffer rubber (middle). These tears can be seen in small cavities in the felt (right). Credit: Matthew Catenacci

To create a flexible wire, the team first sucks a solution of copper nanowires and water through a stencil, creating a stack of interwoven nanowires in the desired shape. The material is similar to the interwoven fibers that comprise fabric felt, but on a much smaller scale, said Wiley, an associate professor of chemistry at Duke.

“The way I think about the wires are like tiny sticks of uncooked spaghetti,” Wiley said. “The water passes through, and then you end up with this pile of sticks with a high porosity.”

The interwoven nanowires are heated to 300 F to melt the contacts together, and then silicone rubber is added to fill in the gaps between the wires.

To show the pliability of their new material, Catenacci patterned the nanowire felt into a variety of squiggly, snaking patterns. Stretching and twisting the wires up to 300 times did not degrade the conductivity.

The material maintains its conductivity when twisted and stretched. Credit: Matthew Catenacci

“On a larger scale you could take a whole shirt, put it over a vacuum filter, and with a stencil you could create whatever wire pattern you want,” Catenacci said. “After you add the silicone, so you will just have a patch of fabric that is able to stretch.”

Their felt is not the first conductive material that displays the agility of a gymnast. Flexible wires made of silver microflakes also exhibit this unique set of properties. But the new material has the best performance of any other material so far, and at a much lower cost.

“This material retains its conductivity after stretching better than any other material with this high of an initial conductivity. That is what separates it,” Wiley said.

Stretchable Conductive Composites from Cu-Ag Nanowire Felt,” Matthew J. Catenacci, Christopher Reyes, Mutya A. Cruz and Benjamin J. Wiley. ACS Nano, March 14, 2018. DOI: 10.1021/acsnano.8b00887

Post by Kara Manke

MRI Tags Stick to Molecules with Chemical “Velcro®”

An extremely close-up view of Velcro

In the new technique, MRI chemical tags attach to a target molecule and nothing else – kind of like how Velcro only sticks to itself. Credit: tanakawho, via Flickr.

Imagine attaching a beacon to a drug molecule and following its journey through our winding innards, tracking just where and how it interacts with the chemicals in our bodies to help treat illnesses.

Duke scientists may be closer to doing just that. They have developed a chemical tag that can be attached to molecules to make them light up under magnetic resonance imaging (MRI).

This tag or “lightbulb” changes its frequency when the molecule interacts with another molecule, potentially allowing researchers to both locate the molecule in the body and see how it is metabolized.

“MRI methods are very sensitive to small changes in the chemical structure, so you can actually use these tags to directly image chemical transformations,” said Thomas Theis, an assistant research professor in the chemistry department at Duke.

Chemical tags that light up under MRI are not new. In 2016, the Duke team of Warren S. Warren’s lab and Qiu Wang’s lab created molecular lightbulbs for MRI that burn brighter and longer than any previously discovered.

A photo of graduate students Junu Bae and Zijian Zhou in front of a bookshelf.

Junu Bae and Zijian Zhou, the co-first authors of the paper. Credit: Qiu Wang, Duke University.

In a study published March 9 in Science Advances, the researchers report a new method for attaching tags to molecules, allowing them to tag molecules indirectly to a broader scope of molecules than they could before.

“The tags are like lightbulbs covered in Velcro,” said Junu Bae, a graduate student in Qiu Wang’s lab at Duke. “We attach the other side of the Velcro to the target molecule, and once they find each other they stick.”

This reaction is what researchers call bioorthogonal, which means that the tag will only stick to the molecular target and won’t react with any other molecules.

And the reaction was designed with another important feature in mind — it generates a rare form of nitrogen gas that also lights up under MRI.

“One could dream up a lot of potential applications for the nitrogen gas, but one that we have been thinking about is lung imaging,” Theis said.

Currently the best way to image the lungs is with xenon gas, but this method has the downside of putting patients to sleep. “Nitrogen gas would be perfectly safe to inhale because it is what you inhale in the air anyways,” Theis said.

A stylized chemical diagram of the hyperpolarization process

In the new technique, a type of molecule called a tetrazine is hyperpolarized, making it “light up” under MRI (illustrated on the left). It is then tagged to a target molecule through a what is called a bioorthogonal reaction. The reaction also generates a rare form of nitrogen gas that can be spotted under MRI (illustrated on the right). Credit: Junu Bae and Seoyoung Cho, Duke University.

Other applications could include watching how air flows through porous materials or studying the nitrogen fixation process in plants.

One downside to the new tags is that they don’t shine as long or as brightly as other MRI molecular lightbulbs, said Zijian Zhou, a graduate student in  Warren’s lab at Duke.

The team is tinkering with the formula for polarizing, or lighting up, the molecule tags to increase their lifetime and brilliance, and to make them more compatible with chemical conditions in the human body.

“We are now developing new techniques and new procedures which may be helpful for driving the polarization levels even higher, so we can have even better signal for these applications,” Zhou said.

15N4-1,2,4,5-tetrazines as potential molecular tags: Integrating bioorthogonal chemistry with hyperpolarization and unearthing para-N2,” Junu Bae, Zijian Zhou, Thomas Theis, Warren S. Warren and Qiu Wang. Science Advances, March 9, 2018. DOI: 10.1126/sciadv.aar2978

Post by Kara Manke

How Earth’s Earliest Lifeforms Protected Their Genes

A colorful hot spring in Yellowstone National Park

Heat-loving thermophile bacteria may have been some of the earliest lifeforms on Earth. Researchers are studying their great great great grandchildren, like those living in Yellowstone’s Grand Prismatic Spring, to understand how these early bacteria repaired their DNA.

Think your life is hard? Imagine being a tiny bacterium trying to get a foothold on a young and desolate Earth. The earliest lifeforms on our planet endured searing heat, ultraviolet radiation and an atmosphere devoid of oxygen.

Benjamin Rousseau, a research technician in David Beratan’s lab at Duke, studies one of the molecular machines that helped these bacteria survive their harsh environment. This molecule, called photolyase, fixes DNA damaged by ultraviolet (UV) radiation — the same wavelengths of sunlight that give us sunburn and put us at greater risk of skin cancer.

“Anything under the sun — in both meanings of the phrase — has to have ways to repair itself, and photolyase proteins are one of them,” Rousseau said. “They are one of the most ancient repair proteins.”

Though these proteins have been around for billions of years, scientists are still not quite sure exactly how they work. In a new study, Rousseau and coworkers, working with Professor David Beratan and Assistant Research Professor Agostino Migliore, used computer simulations to study photolyase in thermophiles, the great great great great grandchildren of Earth’s original bacterial pioneers.

The study appeared in the Feb. 28 issue of the Journal of the American Chemical Society.

DNA is built of chains of bases — A, C, G and T — whose order encodes our genetic information. UV light can trigger two adjacent bases to react and latch onto one other, rendering these genetic instructions unreadable.

Photolyase uses a molecular antenna to capture light from the sun and convert it into an electron. It then hands the electron over to the DNA strand, sparking a reaction that splits the two bases apart and restores the genetic information.

A ribbon diagram of a photolyase protein

Photolyase proteins use a molecular antenna (green, blue and red structure on the right) to harvest light and convert it into an electron. The adenine-containing structure in the middle hands the electron to the DNA strand, splitting apart DNA bases. Credit: Benjamin Rousseau, courtesy of the Journal of the American Chemical Society.

Rousseau studied the role of a molecule called adenine in shuttling the electron  from the molecular antenna to the DNA strand. He looked at photolyase in both the heat-loving ancestors of ancient bacteria, called thermophiles, and more modern bacteria like E. Coli that thrive at moderate temperatures, called mesophiles.

He found that in thermophiles, adenine played a role in transferring the electron to the DNA. But in E. coli, the adenine was in a different position, providing mainly structural support.

The results “strongly suggest that mesophiles and thermophiles fundamentally differ in their use of adenine for this electron transfer repair mechanism,” Rousseau said.

He also found that when he cooled E. Coli down to 20 degrees Celsius — about 68 degrees Fahrenheit — the adenine shifted back in place, resuming its transport function.

“It’s like a temperature-controlled switch,” Rousseau said.

Though humans no longer use photolyase for DNA repair, the protein persists in life as diverse as bacteria, fungi and plants — and is even being studied as an ingredient in sunscreens to help repair UV-damaged skin.

Understanding exactly how photolyase works may also help researchers design proteins with a variety of new functions, Rousseau said.

“Photolyase does all of the work on its own — it harvests the light, it transfers the electron over a huge distance to the other site, and then it cleaves the DNA bases,” Rousseau said. “Proteins with that kind of plethora of functions tend to be an attractive target for protein engineering.”

Post by Kara Manke

Can Science Explain Everything? An Exploration of Faith

The Veritas Forum, Feb. 1 in Penn Pavilion

I found out about this year’s Veritas Forum an hour before it started — a friend, who two years ago helped me explore Christianity (I grew up non-religious and was curious), mentioned it when we ran into each other at the Brodhead Center.

So, to avoid my academic responsibilities, I instead listened to Duke physics professor Ronen Plesser, a non-practicing Jew, Troy Van Voorhis, a Christian who teaches chemistry at MIT, and moderator Ehsan Samei, a professor of radiology and biomedical engineering at Duke. They discussed the God Hypothesis and how it fit in with their views as hard scientists.

Ehsan Samei

As someone who has relied on the scientific method instead of an omniscient, higher power to understand the natural world, I found it amazing how the speakers used relatable examples to demonstrate their belief that humans cannot explain everything. They started answering the classic question “Why is the sky blue?,” using more and more complex chemistry and physics as answers only led to more questions.

At some point, science-based explanations about how and why molecules move the way they do and where they come from didn’t suffice — at some point, it just seems like something, or someone, is responsible for the unexplainable.

Troy Van Voorhis of MIT

Something that Van Voorhis said particularly stuck in my mind. Reproducibility and objectivity form the “bedrock of science,” but are also it’s “grand limitations.” They are essential to corroborating the results of a scientific study or experiment, but can they really confirm something as scientific truth? When does reproducibility adequately overcome variation in data, and can something be defined as truly objective?

So, I sat there in the audience, thinking about alternatives to explaining morals, ethics, and the feeling of being human since, to paraphrase Plesser, science just doesn’t cut it in these cases. He elaborated on faith after branching off Van Voorhis’ point of view. Plesser’s explanation made the overlap of science and religion become more and more prominent. As someone who also does not practice a religion, I felt that his comparison of faith in science and faith in religion comforting.

Ronan Plesser

Even though I still struggle to fully accept Christ, I was aware of the similarities of the path to scientific and spiritual enlightenment. In science, incessant questioning of our surroundings is necessary to understand the Truths of our world (“otherwise we wouldn’t be publishing papers and we would be out of our jobs!”), as are the calls to God to come down and help people improve themselves. It is impossible, then, to avoid faith entirely since being human inherently involves belief in some sort of system.

I was wowed by the connections that the three men were making between the seemingly divergent areas. I was even more astonished, though, by their emphasis on humility. They exemplified the need for understanding and patience when describing scientific theories and religious ideologies. To be humble is to accept that people have differences and to acknowledge these differences is the only way to reduce conflicts between religion and science.

Post by Stella Wang

Farewell, Electrons: Future Electronics May Ride on New Three-in-One Particle

“Trion” may sound like the name of one of the theoretical particles blamed for mucking up operations aboard the Starship Enterprise.

But believe it or not, trions are real — and they may soon play a key role in electronic devices. Duke researchers have for the first time pinned down some of the behaviors of these one-of-a-kind particles, a first step towards putting them to work in electronics.

A carbon nanotube, shaped like a rod, is wrapped in a helical coating of polymer

Three-in-one particles called trions — carrying charge, energy and spin — zoom through special polymer-wrapped carbon nanotubes at room temperature. Credit: Yusong Bai.

Trions are what scientists call “quasiparticles,” bundles of energy, electric charge and spin that zoom around inside semiconductors.

“Trions display unique properties that you won’t be able to find in conventional particles like electrons, holes (positive charges) and excitons (electron-hole pairs that are formed when light interacts with certain materials),” said Yusong Bai, a postdoctoral scholar in the chemistry department at Duke. “Because of their unique properties, trions could be used in new electronics such as photovoltaics, photodetectors, or in spintronics.”

Usually these properties – energy, charge and spin – are carried by separate particles. For example, excitons carry the light energy that powers solar cells, and electrons or holes carry the electric charge that drives electronic devices. But trions are essentially three-in-one particles, combining these elements together into a single entity – hence the “tri” in trion.

A diagram of how a trion is formed in carbon nanotubes.

A trion is born when a particle called a polaron (top) marries an exciton (middle). Credit: Yusong Bai.

“A trion is this hybrid that involves a charge marrying an exciton to become a uniquely distinct particle,” said Michael Therien, the William R. Kenan, Jr. Professor of Chemistry at Duke. “And the reason why people are excited about trions is because they are a new way to manipulate spin, charge, and the energy of absorbed light, all simultaneously.”

Until recently, scientists hadn’t given trions much attention because they could only be found in semiconductors at extremely low temperatures – around 2 Kelvin, or -271 Celcius. A few years ago, researchers observed trions in carbon nanotubes at room temperature, opening up the potential to use them in real electronic devices.

Bai used a laser probing technique to study how trions behave in carefully engineered and highly uniform carbon nanotubes. He examined basic properties including how they are formed, how fast they move and how long they live.

He was surprised to find that under certain conditions, these unusual particles were actually quite easy to create and control.

“We found these particles are very stable in materials like carbon nanotubes, which can be used in a new generation of electronics,” Bai said. “This study is the first step in understanding how we might take advantage of their unique properties.”

The team published their results Jan. 8 in the Proceedings of the National Academy of Sciences.

Dynamics of charged excitons in electronically and morphologically homogeneous single-walled carbon nanotubes,” Yusong Bai, Jean-Hubert Olivier, George Bullard, Chaoren Liu and Michael J. Therien. Proceedings of the National Academy of Sciences, Jan. 8, 2018 (online) DOI: 10.1073/pnas.1712971115

Post by Kara Manke

Glitter and Jell-O Reveal the Science of Oobleck

A black and white image showing a circular disk dropping into a container of oobleck

Mixing black glitter with oobleck allowed researchers to track the movement of individual cornstarch particles after a sudden impact. A computer program locked onto pieces of glitter and illustrated their motion. Credit: Melody Lim.

What do gelatin and glitter have to do with serious science? For some experiments, a lot! Duke alumna Melody Lim used jiggly Jell-O and a just a pinch of glitter to solve a scientific mystery about the curious goo many like to call oobleck.

To the uninitiated, oobleck is almost magic. The simple mixture of cornstarch and water feels solid if you squeeze it, but moments later runs through your fingers like water. You can dance across a bathtub full of oobleck, but stand still for too long and you will be sucked into a goopy mess. Not surprisingly, the stuff is a Youtube favorite.

Oobleck is an example of what scientists call a non-Newtonian fluid, a liquid whose viscosity – how easily it changes shape and flows – depends upon the force that is applied. But exactly how it is that this material switches from solid to liquid and back again has remained a mystery to scientists.

A piece of gelatin being squeezed viewed through a circular polarizer

This blogger mixed up a batch of jello to see the photoelastic effect for herself. When viewed with polarized light – from an iPhone screen and a circular polarizer – the jello changes color when squeezed.

“Water is simple to understand, and so is cornstarch,” said Lim, ’16, who is currently a graduate student at the University of Chicago. “However, a combination of the two produces this ‘liquid’ that ripples and flows, solidifies beneath your feet if you run on it, then turns back into a liquid if you stop running and stand still. I wanted to know why.”

The question beguiling scientists was whether sudden impact causes the cornstarch particles to “jam” into a solid like cement, or whether the suspension remains liquid but simply moves too slowly for its liquid-like properties to be apparent — similar to what happens if you skip a rock off the surface of a lake.

“There are these two opposing pictures,” said Robert Behringer, James B. Duke Professor of Physics at Duke. “Either you squish the material and turn it into cement temporarily, or you simply transmit the stress from the impactor straight to the boundary.”

Lim did two sets of experiments to find out which way oobleck works. In one experiment, she mixed black glitter into a transparent channel filled with oobleck, and then used a high-speed camera to watch how the material responded to the impact. The glitter let her track the motion of individual particles after the disc hit.

A piece of gelatin changes color when you squeeze it.

The photoelastic effect in gelatin.

Her video shows that the particles near the impact site jam and become solid, forming what the researchers call a “mass shock” wave that travels slowly through the suspension.

In a second set of experiments, Lim placed the oobleck in a container lined with gelatin, the main ingredient in Jell-O – besides sugar and food dye, of course. Gelatin is what is called a photoelastic material, which means that applying pressure bends light that travels through it, like a prism.

“Next time you eat Jell-O, get out your sunglasses and get somebody else’s sunglasses and look between them,” Behringer said. “Because if you give it a shake you should see all these stress patterns bouncing around.”

After the metal disc hit the oobleck, the gelatin let Lim see how fast the resulting pressure wave traveled through the material and reached the boundary.

A black and white image showing pressure waves traveling through a transparent material after impact

The researchers poured oobleck into a clear container lined with gelatin, a material that bends light when a pressure is applied to it. They saw that the force of a sudden impact is rapidly transmitted through the oobleck and to the boundary with the gelatin. Credit: Melody Lim.

They found that when the impact is sudden, the pressure wave traveled to the gelatin boundary faster than the “mass shock” wave. This means that the reason oobleck appears solid after a sudden impact is because the force of the collision is quickly transmitted to a solid boundary.

“If you are running across the water, that actually puts you into an impact velocity range where the pressure wave is significantly faster than the mass shock,” Behringer said. “Whereas if you try to walk across it, the impact speeds are slow, and the system actually doesn’t have the ability to transport the momentum quickly through the material and so you just sink in.”

“If you’d told me when I started that I would line a narrow container with Jell-o, add cornstarch, water, and black glitter, drop a piece of metal on it, then publish a paper on the results, I would have laughed at you,” Lim said.

CITATION: “Force and Mass Dynamics in Non-Newtonian Suspensions,” Melody X. Lim, Jonathan Barés, Hu Zheng and Robert P. Behringer. Physical Review Letters, Nov. 3, 2017. DOI: 10.1103/PhysRevLett.119.184501

Post by Kara Manke

Cheating Time to Watch Liquids do the Slow Dance

Colorful spheres simulating liquid molecules shift around inside a cube shape

The team’s new algorithm is able to simulate molecular configurations of supercooled liquids below the glass transition. The properties of these configurations are helping to solve a 70-year paradox about the entropy of glasses. Credit: Misaki Ozawa and Andrea Ninarello, Université de Montpellier.

If you could put on a pair of swimming goggles, shrink yourself down like a character from The Magic School Bus and take a deep dive inside a liquid, you would see a crowd of molecules all partying like it’s 1999.

All this frenetic wiggling makes it easy for molecules to rearrange themselves and for the liquid as a whole to change shape. But for supercooled liquids — liquids like honey that are cooled below their freezing point without crystallizing – the lower temperature slows down the dancing like Etta James’ “At Last.” Lower the temperature enough, and the slow-down can be so dramatic that it takes centuries or even millennia for the molecules to rearrange and the liquid to move.

Scientists can’t study processes that last longer than their careers. But Duke chemists and their Simons Foundation collaborators have found a way to cheat time, simulating the slow dance of deeply supercooled liquids. Along the way, they have found new physical properties of “aged” supercooled liquids and glasses.

A droplet rises above a surface of water

Credit: Ruben Alexander via Flickr.

To understand just how slow deeply supercooled liquids move, consider the world’s longest-running experiment, the University of Queensland’s Pitch Drop Experiment. A single drop of pitch forms every eight to thirteen years — and this pitch is moving faster than deeply supercooled liquids.

“Experimentally there is a limit to what you can observe, because even if you managed to do it over your entire career, that is still a maximum of 50 years,” said Patrick Charbonneau, an associate professor of chemistry and physics at Duke. “For many people that was considered a hard glass ceiling, beyond which you couldn’t study the behavior of supercooled liquids.”

Charbonneau, who is an expert on numerical simulations, said that using computers to simulate the behavior of supercooled liquids has even steeper time limitations. He estimates that, given the current rate of computer advancement, it would take 50 to 100 years before computers would be powerful enough for simulations to exceed experimental capabilities – and even then the simulations would take months.

To break this glass ceiling, the Charbonneau group collaborated with Ludovic Berthier and his team, who were developing an algorithm to bypass these time constraints. Rather than taking months or years to simulate how each molecule in a supercooled liquids jiggles around until the molecules rearrange, the algorithm picks individual molecules to swap places with each other, creating new molecular configurations.

This allows the team to explore new configurations that could take millennia to form naturally. These “deeply supercooled liquids and ultra-aged glasses” liquids are at a lower energy, and more stable, than any observed before.

“We were cheating time in the sense that we didn’t have to follow the dynamics of the system,” Charbonneau said. “We were able to simulate deeply supercooled liquids well beyond is possible in experiments, and it opened up a lot of possibilities.”

Two columns of blue and red spheres represent simulations of vapor-deposited glasses.

Glasses that are grown one layer at a time have a much different structure than bulk glasses. The team used their new algorithm to study how molecules in these glasses rearrange, and found that at low temperatures (right), only the molecules at the surface are mobile. The results may be used to design better types of glass for drug delivery or protective coatings. Credit: Elijah Flenner.

Last summer, the team used this technique to discover a new phase transition in low-temperature glasses. They recently published two additional studies, one of which sheds light on the “Kauzmann paradox,” a 70-year question about the entropy of supercooled liquids below the glass transition. The second explores the formation of vapor-deposited glasses, which have applications in drug delivery and protective coatings.

“Nature has only one way to equilibrate, by just following the molecular dynamics,” said Sho Yaida, a postdoctoral fellow in Charbonneau’s lab. “But the great thing about numerical simulations is you can tweak the algorithm to accelerate your experiment.”

Configurational entropy measurements in extremely supercooled liquids that break the glass ceiling.” Ludovic Berthier, Patrick Charbonneau, Daniele Coslovich, Andrea Ninarello, Misaki Ozawa and Sho Yaida. PNAS, Oct. 24, 2017. DOI: 10.1073/pnas.1706860114

The origin of ultrastability in vapor-deposited glasses.” Ludovic Berthier, Patrick Charbonneau, Elijah Flenner and Francesco Zamponi. PRL, Nov. 1, 2017. DOI: 10.1103/PhysRevLett.119.188002

Post by Kara Manke

Designing Drugs Aimed at a Different Part of Life’s Code

Individual RNA molecules fluoresce inside a breast cancer cell.

Individual RNA molecules fluoresce inside a breast cancer cell. Credit: Sunjong Kwon, Oregon Health & Science University, via Flickr.

Most drugs work by tinkering with the behavior of proteins. Like meddlesome coworkers, these molecules are designed to latch onto their target proteins and keep them from doing what they need to do.

If a protein is responsible for speeding up a reaction, the drug helps slow the reaction down. If a protein serves as a gatekeeper to a cell, regulating what gets in and what stays out, a drug changes how many molecules it lets through.

But proteins aren’t the only doers and shakers in our bodies. Scientists are finding that strings of RNA — known primarily for their role in shuttling genetic information from nucleus-bound DNA to the cell’s protein-manufacturing machinery — can also play a major role in regulating disease.

A portrait of Amanda Hargrove

Amanda Hargrove is an assistant professor of chemistry at Duke University.

“There has been what some people are calling an RNA revolution,” said Amanda Hargrove, assistant professor of chemistry at Duke. “In some diseases, non-coding RNAs, or RNAs that don’t turn into protein, seem to be the best predictors of disease, and even to be driving the disease.”

Hargrove and her team at Duke are working to design new types of drugs that target RNA rather than proteins. RNA-targeted drug molecules have the potential help treat diseases like prostate cancer and HIV, but finding them is no easy task. Most drugs have been designed to interfere with proteins, and just don’t have the same effects on RNA.

Part of the problem is that proteins and RNA have many fundamental differences, Hargrove said. While proteins are made of strings of twenty amino acids that can twist into myriad different shapes, RNA is made of strings of only four bases — adenine, guanine, cytosine and uracil.

“People have been screening drugs for different kinds of RNA for quite a while, and historically have not had a lot of success,” Hargrove said. “This begged the question, since RNA has such chemically different properties than proteins, is there something different about the small molecules that we need in order to target RNA?”

To find out, graduate student Brittany Morgan and research associate Jordan Forte combed the scientific literature to identify 104 small molecules that are known interact with specific types of RNA. They then analyzed 20 different properties of these molecules, and compared their properties to those of collections of drug molecules known to interact with proteins.

The team found significant differences in shape, atomic composition, and charge between the RNA-active molecules and the protein-active molecules. They plan to use the results to compile a collection of molecules, called a library, that are chosen to better “speak the language” of the RNA-active molecules. They hope this collection of molecules will be more likely to interact with RNA in therapeutically beneficial ways.

“We found that there are differences between the RNA-targeted molecules and the protein-targeted drugs, and some of them are pretty striking,” Hargrove said. “What that means is that we could start to enrich our screening libraries with these types of molecules, and make these types of molecules, to have better luck at targeting RNA.”

Discovery of Key Physicochemical, Structural, and Spatial Properties of RNA-Targeted Bioactive Ligands.” Brittany S. Morgan, Jordan E. Forte, Rebecca N. Culver, Yuqi Zhang and Amanda Hargrove. Angewandte Chemie, Sept. 18, 2017. DOI: 10.1002/anie.201707641

Kara J. Manke, PhDPost by Kara Manke

Lab-Made Protein Chomps Co-Factor Like a Big Ol' Gator

A protein is illustrated to look like an alligator mouth

The synthetic protein clamps down on the porphyrin like the jaws of an alligator. Credit: Nicholas Polizzi.

Proteins have the power to turbo-charge biochemical reactions inside the body.

Without the help of types of proteins called enzymes, the reaction that builds DNA could take over 130,000 years to complete. Enzymes cut that time down to just a few milliseconds.

To rev up chemical reactions, many proteins team up with smaller molecules or metals called cofactors. Chemists would like to design proteins that bind to non-biological cofactors in order to speed up chemical reactions not found in nature. But first, they have to figure out how to create man-made proteins that attach to new cofactors in exactly the right way, and that is no easy feat.

A team of chemists at Duke and UC San Francisco is the first to solve this protein design puzzle. The team created a synthetic protein that tightly binds a non-biological catalyst, a type of molecule called porphyrin that is capable of stealing electrons from other molecules when it absorbs light.

“To be able to combine man-made catalysts with proteins would be really big in the chemistry field because then you could combine the power of an enzyme with that of a reaction that isn’t found in nature,” said former Duke graduate student Nicholas Polizzi, who is now a postdoctoral researcher in William DeGrado’s lab at UCSF.

“We were able to figure out the design criteria necessary to place that porphyrin in a protein to within a very high accuracy,” Polizzi said. “That was a really big stepping stone to be able to design new protein-cofactor combinations not seen in nature.”

Proteins are made of chains of hundreds or thousands of smaller amino acids that twist and loop into complex 3-D shapes that can interlock with other molecules like pieces of a jigsaw puzzle. To catalyze chemical reactions, protein-cofactor combinations hold two or more molecules in precisely-shaped pockets that keep the molecules in just the right positions, and provide the right environment, for a chemical reaction to occur.

An illustration of a protein jigsaw puzzle

Chemists at Duke and UCSF designed a synthetic protein that tightly binds a non-biological molecule. Credit: Nicholas Polizzi.

Millions of years of evolution have created proteins that fold into the shapes that tightly grip specific cofactors and provide the perfect environments to catalyze chemical reactions.

For over 25 years, chemists have used what they know about protein folding to design synthetic amino acid sequences that twist up into useful shapes. But so far, they have been unable to design a protein that binds a non-biological cofactor with the precision necessary to power complex new chemical reactions.

Polizzi said this may be because these designs focused primarily on the “binding site” where cofactors and reacting molecules fit into the protein, while ignoring the rest of the structure. “What I did differently is that I considered essentially the entire interior of protein as the binding site for the porphyrin, as opposed to just a few amino acids that touch the porphyrin,” Polizzi said.

To understand how this works, you can think of the protein as the mouth of an alligator, said Michael Therien, William R. Kenan Jr. Professor of Chemistry at Duke. The protein latches onto a cofactor in the same way that an alligator uses its front teeth to chomp down on dinner. But for the front teeth to get a strong grip, the jaw and back teeth also have to be designed correctly.

“The new concept here is that the non-binding region of the protein is held in a shape that allows the binding region to work,” Therien said.

“We called the protein ‘gator’ in the lab,” Polizzi said.

The jaws of the gator protein actually clamp down so hard on the porphyrin cofactor that the whole structure is too rigid to catalyze a reaction, Polizzi said. But with a few tweaks to loosen up the structure, he thinks he can get it to work.

“In this reaction, often times you need a little bit of wiggle room in the protein for it to move. And there was no wiggle room in our protein, everything fit too perfectly,” Polizzi said.

CITATION: “De novo design of a hyperstable non-natural protein-ligand complex with sub-A accuracy.” Nicholas F. Polizzi, Yibing Wu, Thomas Lemmin, Alison M. Maxwell, Shao-Qing Zhang, Jeff Rawson, David N. Beratan, Michael J. Therien and William F. DeGrado. Nature Chemistry, Aug. 21, 2017. DOI: 10.1038/nchem.2846

Kara J. Manke, PhDPost by Kara Manke

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