There ’s no gentle response for HIV ; the knavish virus uses our own immune cells to its advantage and mutates readily to shrug off round after round of anti - retrovirals . But thanks to the efforts researchers from the University of Illinois and some wakeless - duty number grind from one of the world ’s fastest petaflop supercomputer , we may be able to block HIV right in its runway .
The latest line of attack against HIV targets its viral casing ( or capsid ) . Capsids lie between the virus ’s spherical outer coat , a .1 micron diameter , lipoid - based layer known as the viral envelope , and a slug - regulate inner coat known as the viral essence that contains the strands of HIV RNA . Capsids comprise 2,000 copies of the viral protein , p24 , arranged in a lattice structure ( a rough insight glean only from days of cryo - negatron microscopy , atomic charismatic resonance spectroscopic analysis , cryo - pica em tomography , and cristal - beam of light crystallography workplace ) . The capsid is responsible for protect the RNA loading , disabling the master of ceremonies ’s immune system of rules , and have the RNA into Modern cells . In other words : It ’s the evil Einstein .
The lattice protein bodily structure allows the capsid to open and near like aHoberman Sphere .
As Dr Peijun Zhang , project lead and associate professor in geomorphological biology at the University of Pittsburgh School of Medicine explain to the BBC :
The capsid is critically important for HIV replication , so knowing its bodily structure in detail could head us to new drugs that can treat or foreclose the infection . The capsid has to stay on intact to protect the HIV genome and get it into the human cell , but once inside , it has to come apart to free its content so that the computer virus can copy . Developing drug that make capsid disfunction by forbid its fabrication or disassembly might stop the virus from reproducing .
But until very late , the precise complex body part — how the chiliad of copy of p24 actually ensnarl together — remained a mystery . The capsid ’s ( comparatively ) large size , non - symmetric soma , protein structure has stumped researchers ’ attempts to efficaciously model it . Earlier research had reveal that the p24 arranged itself in either a pentagon or hexagon shape as part of the capsid body structure , but how many of each and how the piece fit together remained out of reach because science simply did n’t have the computational artistry to pattern this unbelievably complex subatomic structure in atomic - level detail .
This job need a petaflop - degree supercomputer to solve , a class of car that has only recently become readily useable . The team turned to National Center for Supercomputing Applications at the University of Illinois at Urbana - Champaign and its resident supercomputer , Blue Waters .
The team run electron microscopy data collected in lab experiment conducted at the University of Pittsburgh and Vanderbilt University into Blue Waters and permit the $ 108 million , 11.5 petaflop machine do its thing : Crunch massive amounts of information with its 49,000 AMD CPUs . Blue Waters can treat one quadrillion float level operations every second , so sew together together 1,300 protein into an oblong molecular association football ball was no sweat .
The squad developed a novel formation algorithm for the task , dubbed molecular dynamic flexible fitting . “ You essentially simulate the physical characteristics and behavior of large biological molecules , but you also integrate the data into the simulation so that the role model actually drives itself toward accord with the data , ” said Professor Klaus Schulten of the University of Illinois in a closet release .
“ This is a big structure , one of the biggest structure ever solved , ” Schulten continued . “ It was very clear that it would command a huge amount of simulation — the large model ever publish — involving 64 million molecule . ”
The squad reveal the complete capsid structure in aNaturereport yesterday :
The mature human immunodeficiency virus-1 ( HIV-1 ) mirid is best depict by a ‘ fullerene cone ’ model , in which hexamers of the capsid protein are linked to constitute a hexagonal surface grille that is come together by incorporating 12 capsid - protein pentamers .
In all , the HIV capsid requires 216 protein hexagon and 12 protein Pentagon to function — arranged exactly as the predictive models say they would be . The new breakthrough reveals a stunningly various protein in p24 . The protein itself is very whether it ’s shaped into a pentagon or a hexagon , only the attachment sites between p24 protein varies between shapes . How that forge persist a secret .
“ How can a undivided type of protein form something as varied as this matter ? The protein has to be inherently flexible , ” said Schulten .
New question apart , this discovery illustrates precisely how the capsid works and how scientists can best assail that function to disrupt the virus ’ power to reduplicate . By exploiting the capsid ’s structure , researchers theoretically could deliver a molecular padlock that preclude the viral core group from opening and the computer virus from spreading . This discovery could result to an totally unexampled retinue of treatment alternative and could finally outpace HIV ’s ability to chop-chop develop electrical resistance to current enzyme - based medication .
“ The big problem with HIV is that it evolves so apace that any drug you expend you get drug impedance which is why we use a multi - drug cocktail , ” Professor Simon Lovell , a structural biologist at the University of Manchester , said . “ This is another quarry , another matter we can go after to develop a fresh class of drugs to operate alongside the survive stratum . ”
It ’s only a matter of prison term until HIV go the way of polio . And it ’s thanks in no modest part to one beast of a electronic computer . [ BBC – CNet – Nature – University of Illinois – National Science Foundation – NIH – Top Image : CDC ( public domain ) – Trio and duo Images : Theoretical and Computational Biophysics Group ( www.ks.uiuc.edu ) , Beckman Institute for Advanced Science and Technology , UIUC – down Waters : kosheahan/ Flickr – Pipes : UIUC – Illustration : NIAID ]
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