Scientists at Sandia National Laboratories and M.I.T. have created the first computer simulation that successfully models how protein misfolding can occur. Protein misfolding is theorized to turn normally benign proteins into toxic aggregates and cause various types of disease, including Alzheimer's. The key was to recognize that the process could not be modeled by simulating a single protein, but required simulation of two proteins interacting with each other. The new approach revealed that the random distribution of hydrophilic and hydrophobic amino acids within a protein chain helps prevents aggregation with nearby proteins. In an aqueous solution, hydrophilic sequences attract one another and herd the hydrophobic regions into the center. "A protein that violates this quality of apparent randomness tends to aggregate with other proteins to form inert lumps," says Sandia's Sorin Istrail. "Our next project is to apply our system to uncover clues about the mechanism of misfolding that occurs in Alzheimer's." A paper describing the work will be published this spring in the Journal of Computational Biology.—June Kinoshita
Story and visuals available at http://www.sandia.gov/media/fold.htm
Sandia computational biology project: http://www.cs.sandia.gov/~scistra/tortilla.html.
No Available Further Reading
- Istrail S, Schwartz R, King J. Lattice simulations of aggregation funnels for protein folding. J Comput Biol. 1999 Summer;6(2):143-62. PubMed.