This week, a new paper described how researchers pieced together the entire molecular structure of the protein shell of the HIV virus using GPU-based simulations. This remarkable achievement not only paves the way for new therapeutic approaches to AIDs, but establishes GPUs as franchise players in molecular simulation.

In order to photograph really small things, like viruses, they need to be imaged with electrons rather than light. Even electron microscopy (EM) has its limits though, and to see the structure of the proteins that make up a virus, X-rays are the probe of choice. While X-ray crystallography allows researchers to understand the configuration of an individual protein, the way those proteins are assembled to build the virus is still largely invisible to us. The only way to get a picture of what might be going on in this gray area in the middle is to feed massive computer simulations with data from both ends of the process.

To determine the structure of the HIV protein coat (also know 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 EM 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 (much like exterior of a soccer ball or buckyball). 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.

Molecular dynamics simulations apply the laws of motions to individual atoms. They include the attractive and repulsive electromagnetic forces which act on the particle to create their complex motion. To run the model, space and time are discretized — split up into small digital intervals — and the forces are recalculated each time the simulation proceeds through the next iteration.

The researchers adapted an open-source dynamics package known as NAMD (Not just Another Molecular Dynamics program) to run on the GPU cluster. The code was written using the Charm++ parallel programming language known for its efficiency in simulating millions of particles together.

The main job of the capsid coat is to protect the virus when it is between cell hosts. Once inside a cell, it needs to be able to flex open to release the genetic assault machinery of the virus. Anti-capsid drugs have been developed for other viruses but as of yet, none exist for HIV. Understanding how the HIV capsid is assembled will make it easier to develop new drugs which cause premature opening of the capsid, or perhaps block its opening altogether.

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Research paper: doi:10.1038/nature12162 – “Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics”