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Supercomputers help to assemble proteins



  Using supercomputers, scientists just start designing proteins that are pooled to combine and resemble life-giving molecules like hemoglobin. Yours sincerely: Taylor and others.
Red blood cells are incredible. They take oxygen from our lungs and carry it all over our body to keep us alive. The hemoglobin molecule in the red blood cells transports oxygen by changing its shape in one way or another. Four copies of the same hemoglobin protein are opened and closed like flower petals, structurally matched to meet each other. Using supercomputers, scientists are just beginning to design proteins that are pooled to combine and resemble life-giving molecules such as hemoglobin. Scientists claim that their methods can be applied to useful technologies such as pharmaceuticals, artificial energy collection, "intelligent" sensory and building materials, and more.
The scientists have done this work by overcharging proteins, which means they have changed the protein subunits, the amino acids, to give the protein an artificially high positive or negative charge. Using proteins derived from jellyfish, scientists managed to gather a complex sixteen protein structure composed of two stacked octamers, only accumulated, findings that were reported in January 201[ads1]9 in the journal </i>. The team then used supercomputer simulations to validate and inform these experimental results. The supercomputer distributions of Stampede2 at the Texas Advanced Center (TACC) and the comet at the San Diego supercomputer center (SDSC) were awarded to the researchers through XSEDE, Extreme Science and Engineering Discovery Environment, funded by the National Science Foundation (NSF). 19659005] "We found that by taking proteins that normally do not interact with each other, we can make copies that are either very positive or highly negatively charged," says study co-researcher Anna Simone, a PhD student at Ellington's UT Austin Lab. "By combining strongly positively and negatively charged copies, we can make proteins gather in very specific structured groups," Simon said. Scientists call their "super-charged protein assembly" strategy where they manage certain protein interactions by combining engineering variants with compression. </p>
<p>  "We used a very well-known and basic principle of nature that the opposite charges attract," the study added. author Jens Glazer. Glaser is an assistant researcher at Glotzer Group, Department of Chemical Engineering at the University of Michigan. "Ana Simon's group found that when they mix these loaded variants of green fluorescence protein they get highly ordered structures, a real surprise," says Glazer. </p>
<p>  The octamer structure looks like a knitted ring. It consists of 16 proteins – two interlaced rings of eight that interact in very specific, discrete spots. "The reason why it is so difficult to make proteins that interact synthetically is that making these interacting spots and aligning them so they allow proteins to get together in larger, regular structures is very difficult, "Simon explained. They have encountered the problem by adding a lot of positive and negative charges to develop green fluorescence protein (GFP) variants, a well-studied protein from laboratory mouse obtained from the jellyfish of Aequorea victoria </p>
<p>. cellulose fluorescent protein (Ceru) +32, there were additional possibilities for interaction with the negatively charged GFP-17 protein. "By giving these proteins all these options, these different places where they could potentially interact, they were able to choose the most appropriate," Simon said. "There were some patterns and interactions that were there, available and vigorously preferred that they had not had to predict in advance that they would allow them to come together in these particular forms." To obtain engineered fluorescent proteins, Simon and co-authors Arti Pothukuchy, Jimmy Gollihar and Barrett Morrow encoded their genes, including a chemical label used to purify portable DNA fragments called plasmids in E. coli, then gathered the markings a protein that grows E. coli. Scientists mixed proteins together. Initially, they believe that proteins can interact to form large, irregularly structured lumps. "But then, what we were still seeing was this strange, funny peak about 12 nanometers, which was much smaller than a large bunch of proteins but significantly larger than the single protein," Simon said. of the particles that are formed using the Zetasizer tool at the Texas Materials Institute at UT Austin, and verify that the particles contain both Förster Resonance Energy Transfer (FRET) cellulose and GFP proteins that measure the transfer of energy between different color fluorescent proteins , producing fluorescence in response to different light energies to see if they are close together. Negative spot electron microscopy identifies the specific particle structure conducted by David Taylor, assistant professor of molecular biology at UT Austin. It showed that the 12 nm particle consisted of ordered octamers comprised of sixteen proteins. "We found them to be these beautifully formed flower structures," Simon said. [2] [2] [2] [2] [2] [2] [2] [2] [2] [2] [2] [2] [2] [2] [2] [2] [2] [2] [2] [2] [2] [2] [2] [5]  a supercomputer at San Diego's supercomputer center (left) and a Stampede2 supercomputer at the Texas Advanced Center (right). Credit: SDSC, TACC<br />
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<p>  Computational modeling improves the measurement of how proteins are arranged in a clear picture of the beautiful, colorful structure, according to Jens Glazer. "We had to invent a model that is complex enough to describe the physics of charged green fluorescent proteins and present all the relevant atomic details, but it is efficient enough to be able to simulate this on a realistic time scale. The model would have taken us more than a year to get a computer simulation from the computer, no matter how fast the computer is, "Glaser said. </p>
<p>  They simplified the model by reducing the resolution without sacrificing important details of interactions between proteins. , "That's why we used a model where the shape of the protein is accurately represented by a molecular surface, just like the one measured by the crystallographic structure of the protein," Glazer added. and to improve what we were able to get out of our simulations, were cryo-EM data, "said Vass Ramasubramani, a graduate of the Chemical Engineering student at the University of Michigan. "It really helped us find the optimal configuration we put into these simulations that then helped us to confirm the stability arguments we were doing and we hope to continue to make predictions about ways we can destabilize or change this structure, "said Ramasubramani. </p><div><script async src=

Scientists needed a lot of computational power to make the scale calculations they wanted.

"We used XSEDE to take these huge systems where there are many different parts interacting with each other, and we calculate everything about it at once, so when you start moving your system ahead with some likeness of time, you can get a clue "If you try to do the same kind of simulation we did on a laptop, it would take months, if not years, to figure out if I understand if a structure will be be stable. We can not use XSEDE for us, where you could use essentially 48 cores, 48 ​​computing units at a time to make these calculations very parallel, and we would do so much more slowly. "

The TACC Stampede2 supercomputer contains 4,200 Intel Knights Landing and 1,736 Intel Skylake X computing nodes, each Skylake node having 48 cores, the main unit of the computer processor." The Stampede2 Supercomputer Skeleton Units were key to delivering the performance needed to calculate these electrostatic interactions that act between oppositely charged proteins in an effective way, "said Glaser." The presence of a Stampede2 supercomputer was just at the right time to be able to perform these simulations. "

Initially, the science gauge is testing its simulations on the Comet system in SDSC. "When we first discovered what model to use and whether this simplistic model would give us reasonable results, Comet was a great place to try these simulations," said Ramasubrama. a test of what we do. "

If we look at the larger scientific picture, scientists hope that this work will contribute to understanding why so many proteins in nature will oligomerize or merge to form more complex and interesting.

"We have shown that there is no need for a very specific, predetermined set of plans and interactions to form these structures," Simon said. "This is important because it means that maybe, and quite likely, we can pick up other groups of molecules that we want to do oligomerization and generate both positively charged and negatively charged variants, combine them and have specially ordered structures for them."

] Natural biomaterials like bones, feathers and shells can be healthy but light. "We think the assembly of supercharged proteins is an easier way to develop the kind of materials that have exciting synthetic properties without having to spend so much time or know exactly how they will get together in advance," Simon said. "We believe this will accelerate the ability to engineer synthetic materials and to detect and study these nanostructured protein materials."

The study "Super-Cutting Allows Organized Collection of Synthetic Biomolecules" was published in the journal in January 2019.


Scientists are forcing proteins to form synthetic structures with a method that mimics nature


More Information:
Anna J. Simon et al., Supercharging allows organized assembling of synthetic biomolecules, Nature Chemistry (2019). DOI: 10.1038 / s41557-018-0196-3

Provided by
Texas University in Austin

References :
Supercomputers help to assemble the supercharged protein
drawn up on 30 March 2019
from https://phys.org/news/2019-03-supercomputers-supercharge-protein.html

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