In an article entitled, ‘Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics,’ published in May 29, 2013, issue of Nature (doi:10.1038/nature12162), the lead author Gongpu Zhao with nine other associates from six different institutes have used a supercomputer to map the structure of the protein that makes up the HIV capsid (the virus’s protein casing that holds its DNA). The capsid has to be strong enough to protect the virus outside of a host cell, but pliable enough to break open when the virus infects a cell so that the contents can be released for the virus to replicate in the host cells. Scientists have tried to find ways to attack HIV’s capsid, but it has proved to be too tough. Moreover, HIV mutates very quickly, making it resistant to almost every antiviral drug. By targeting the capsid rather than its DNA, researchers believe the virus will not develop drug resistances as quickly. Developing drugs that cause capsid dysfunction by preventing its assembly or disassembly might stop the virus from reproducing. This approach has the potential to be a powerful alternative to our current HIV therapies, which work by targeting certain enzymes.

To determine the structure of the HIV protein coat (also known as the capsid), the researchers ran simulations at the petascale level using the Blue Waters supercomputer at the University of Illinois. This machine has some 237 Cray XE6 cabinets, and 32 Cray XK7 cabinets utilizing Nvidia Tesla Kepler GPU computing capability. At a quadrillion operations per second, 100 nanoseconds of detailed molecular motion could be simulated on the 1300 identical proteins that make up the capsid. Data was used from an Electron Microscope imaging technique known as ‘cryoelectron tomography’ to determine the structure of the HIV core. At eight angstrom resolution, a rough layout of the overlying capsid shell could be obtained. It was already known that the capsid proteins tend to form hexamers and pentamers. By contrast, the HIV virion was known to have an asymmetrical form, and it has also been established that many viruses have some variance in the stable structures they can assume. The researchers were able to simulate 64 million atoms and determine that the capsid structure contains 216 hexamers and 12 pentamers. However, the process revealed critical interactions between molecules in areas that are necessary for the shell’s assembly and stability. These potential vulnerabilities in the protective coat of the viral genome could be exploited by scientists designing new drugs to tackle the problem of HIV resistance. [summarized by a graduate student, Samsad Razzaque at pbtlabdu.net.]