Wit, grit and a supercomputer yield chemical structure of HIV capsid
May 29, 2013 ? A team led by researchers at the University of Pittsburgh School of Medicine has described for the first time the 4-million-atom structure of the HIV's capsid, or protein shell. The findings, highlighted on the cover of the May 30 issue of Nature, could lead to new ways of fending off an often-changing virus that has been very hard to conquer.
Scientists have long struggled to decipher how the HIV capsid shell is chemically put together, said senior author Peijun Zhang, Ph.D., associate professor, Department of Structural Biology, University of Pittsburgh School of Medicine.
"The capsid is critically important for HIV replication, so knowing its structure in detail could lead us to new drugs that can treat or prevent the infection," she said. "This approach has the potential to be a powerful alternative to our current HIV therapies, which work by targeting certain enzymes, but drug resistance is an enormous challenge due to the virus' high mutation rate."
Previous research has shown that the cone-shaped shell is composed of identical capsid proteins linked together in a complex lattice of about 200 hexamers and 12 pentamers, Dr. Zhang said. But the shell is non-uniform and asymmetrical; uncertainty remained about the exact number of proteins involved and how the hexagons of six protein subunits and pentagons of five subunits are joined. Standard structural biology methods to decipher the molecular architecture were insufficient because they rely on averaged data, collected on samples of pieces of the highly variable capsid to identify how these pieces tend to go together.
Instead, the team used a hybrid approach, taking data from cryo-electron microscopy at an 8-angstrom resolution (a hydrogen atom measures 0.25 angstrom) to uncover how the hexamers are connected, and cryo-electron tomography of native HIV-1 cores, isolated from virions, to join the pieces of the puzzle. Collaborators at the University of Illinois then used their new Blue Waters supercomputer to run simulations at the petascale, involving 1 quadrillion operations per second, that positioned 1,300 proteins into a whole that reflected the capsid's known physical and structural characteristics.
The process revealed a three-helix bundle with critical molecular interactions at the seams of the capsid, areas that are necessary for the shell's assembly and stability, which represent vulnerabilities in the protective coat of the viral genome.
"The capsid is very sensitive to mutation, so if we can disrupt those interfaces, we could interfere with capsid function," Dr. Zhang said. "The capsid has to remain intact to protect the HIV genome and get it into the human cell, but once inside it has to come apart to release its content so that the virus can replicate. Developing drugs that cause capsid dysfunction by preventing its assembly or disassembly might stop the virus from reproducing."
The project was funded by National Institutes of Health grants GM082251, GM085043 and GM104601 and the National Science Foundation.
"By using a combination of experimental and computational approaches, this team of investigators has produced a clearer picture of the structure of HIV's protective covering," said the National Institutes of Health's Michael Sakalian, Ph.D., who oversees this and other grants funded through an AIDS-related structural biology program. "The new structural details may reveal vulnerabilities that could be exploited by future therapeutics."
Source: http://feeds.sciencedaily.com/~r/sciencedaily/~3/tMgcKXARwnE/130529133403.htm
warren sapp i robot the big c the visitor king of kings ostara masters 2012
posted by rosamei38 @ 8:20 PM
0 Comments
Today, Google has updated its Google+ app for Android to get up to speed with all of the changes announced during last week’s I/O Developers conference. In all, there were 41 new updates including a brand new stream, photos experience and of course Hangouts. The Android version has all of that, and one brand new feature, a new location section. Where the Anroid app really shines is with the photo capabilities. The updated Google+ app now has the auto backup, highlight, enhance and “auto awesome” functionality that the desktop version has. It’s be really handy to be able to enhance your photos directly within the app, rather than waiting until you get back to your computer or relying on Google to do its magical synthetic wrinkle removal, even though it’s cool. To make it easier to “make plans and meet,” Google+ has broken “Locations” out into its own section. Now, when you share your location with certain Circles, your friends can easily find you by tapping on that section. Naturally, it drops everyone’s location onto a Map, which makes it pretty seamless: Location is something that hasn’t been a great piece of Google+ to date. The service currently picks up where you are and asks you for your explicit location, not really telling you who will get to see it. With the Location section and controls, its easier to manage and can turn into an experience similar to that of Foursquare. The stream is getting all of the features from last week, too. The autohashtags will let you drill into new content, hopefully sucking up all of your free time. It turns the Google+ experience into something like Wikipedia, where you can just keep tapping on relevant content and hopefully find some new people to follow along the way. While you’re not going to get the new three-column layout on your smartphone, the drilling down is actually fun. We’ll await the iOS update, but expect the same items to find their way into that version. All of these enhancements are made to entice you to do a little bit more in Google+, as the company doesn’t really expect you to jump ship from one network to another. The features are more complimentary to one another in this update, giving a better experience to new users, which is the most important demographic for Google to focus on right now. Those of
May 15, 2013
