Posted 18 July 2007 - 01:08 PM
The Science of Folding@Home
from the F@H website:
WHAT ARE PROTEINS?
Proteins are necklaces of amino acids --- long chain molecules. Proteins are the basis of how biology gets things done. As enzymes, they are the driving force behind all of the biochemical reactions which make biology work. As structural elements, they are the main constituent of our bones, muscles, hair, skin and blood vessels. As antibodies, they recognize invading elements and allow the immune system to get rid of the unwanted invaders. For these reasons, scientists have sequenced the human genome -- the blueprint for all of the proteins in biology -- but how can we understand what these proteins do and how they work?
RELATIONSHIP TO THE HUMAN GENOME PROJECT
Since proteins play such fundamental roles in biology, scientists have sequenced the human genome. The genome is in a sense a "blueprint" for these proteins -- the genome contains the DNA code which specifies the sequence of the amino acids beads along the protein "necklace."
WHY DO PROTEINS "FOLD"?
However, only knowing this sequence tells us little about what the protein does and how it does it. In order to carry out their function (eg as enzymes or antibodies), they must take on a particular shape, also known as a "fold." Thus, proteins are truly amazing machines: before they do their work, they assemble themselves! This self-assembly is called "folding."
One of our project goals is to simulate protein folding in order to understand how proteins fold so quickly and reliably, and to learn how to make synthetic polymers with these properties. Movies of the results of some of these simulation results can be found here.
PROTEIN FOLDING AND DISEASE: BSE (Mad Cow), Altzheimer's, ...
What happens if proteins don't fold correctly? Diseases such as Alzheimer's disease, cystic fibrosis, BSE (Mad Cow disease), an inherited form of emphysema, and even many cancers are believed to result from protein misfolding.
When proteins misfold, they can clump together ("aggregate"). These clumps can often gather in the brain, where they are believed to cause the symptoms of Mad Cow or Alzheimer's disease.
PROTEIN FOLDING AND NANOTECHNOLOGY: Building man made machines on the nanoscale
In addition to biomedical applications, learning about how proteins fold will also teach us how to design our own protein-sized "nanomachines" to do similar tasks. Of course, before nanomachines can carry out any activity, they must also be assembled.
WHY IS PROTEIN FOLDING SO DIFFICULT TO UNDERSTAND?
It's amazing that not only do proteins self-assemble -- fold -- but they do so amazingly quickly: some as fast as a millionth of a second. While this time is very fast on a person's timescale, it's remarkably long for computers to simulate.
In fact, it takes about a day to simulate a nanosecond (1/1,000,000,000 of a second). Unfortunately, proteins fold on the tens of microsecond timescale (10,000 nanoseconds). Thus, it would take 10,000 CPU days to simulate folding -- i.e. it would take 30 CPU years! That's a long time to wait for one result!
A SOLUTION: DISTRIBUTED DYNAMICS
To solve the protein folding problem, we need to break the microsecond barrier. Our group has developed multiple new ways to simulate protein folding which can break the microsecond barrier by dividing the work between multiple processors in a new way -- with a near linear speed up in the number of processors. Thus, with power of Folding@Home (over 100,000 processors), we have successfully smashed the microsecond barrier, simulating milliseconds of folding time and helped to unlock the mystery of how proteins fold.
WHAT HAVE WE DONE SO FAR AND WHERE ARE WE GOING?
Folding@Home has been a success. We have folded several small, fast folding proteins, with experimental validation of our method. We are now working to further develop our method, and to apply it to more complex and interesting proteins and protein folding and misfolding questions.
Since then, Folding@Home has studied more complex proteins, reporting on the folding of many proteins on the microsecond timescale, including BBA5, the villin headpiece, Trp Cage, among others.
More recently, we have been putting a great deal of effort into studying proteins relevant for diseases, such as Alzheimer's, Hunntington's, and Osteogenesis Imperfecta.