Efforts to understand protein folding and unfolding could lead to treatments for a wide range of misfolding diseases.

Proteins are the molecules of life. They form the framework of our muscular systems and other tissues, serve as antibodies, function as hormones, and perform many other vital tasks in the human body. Proteins are also the enzymes that carry out most of the chemical reactions in the human body.

Each protein comes from a different gene sequence. The sequence determines the structure of each individual protein. There are an astronomical number of three-dimensional configurations that proteins can form--scientists estimate that there may be more possible structures than the number of grains of sand on a beach. Because proteins derive their functionality from their structure, which is based on their gene sequence, each gene sequence produces a different kind of protein destined to complete a unique task.

However, surprisingly little is known about the physical structures of proteins and how they are created from those gene sequences. Scientists know that proteins undergo processes called folding and unfolding through which they are built and torn down, but they don't know how or why naturally occurring proteins consistently display a particular shape, or native state, after the folding process.

Finding out why proteins fold into a consistent native state is important because occasionally the natural folding process breaks down and the proteins form the wrong structures. When that happens, the proteins' functions suffer--DNA may not replicate properly or drugs sporting proteins as main components may not work. Protein misfolding diseases, such as bovine spongiform encephalopathy (Mad Cow disease), Parkinson's, or Alzheimer's, can occur.

To prevent proteins from misfolding and causing serious problems, scientists need to know more about why they fold and unfold the way they do. If researchers could discover what stimuli cause certain structures to appear, new solutions to protein misfolding diseases, such as structure-based drugs and a better understanding of gene mutations, could be possible.

Carlos Simmerling, a professor of biochemistry at Stony Brook University in New York, and a team of students and colleagues are working to understand why proteins fold and unfold and what happens during the process. Using NCSA's Tungsten and Platinum supercomputing clusters, they are simulating the folding and unfolding processes of small proteins and comparing their findings to experimental results from other research groups.

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Access Online | Posted 1-11-2005