HIV STRUCTURE CRACKED USING GPU-BASED STIMULUS

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
performed 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.