Folding Forum

Advances in computing technology.
Understanding protein folding was a key motivation for IBM’s development of the Blue Gene supercomputer (45), now also used to study the brain, materials, weather patterns, and quantum and nuclear physics. Protein folding has also driven key advances in distributed-grid computing, such as in Folding@home, developed by Pande at Stanford, in which computer users all over the world donate their idle computer time to perform physical simulations of protein systems (46). Folding@home, which now has more than one million registered users and an average of 200,000 user-donated CPUs available at any one time, provided some of the earliest simulations showing that MD simulations can accurately predict folding rates (47). The Anton computer from DE Shaw Research, custom designed to simulate biomolecules, gives several orders of magnitude better performance than conventional computers (48). Advances in computer technology have led to major advances in forcefields and to more reliable atomic-level insights into biological mechanisms.

Summary

Fifty years ago, the protein-folding problem was born as a grand challenge of basic science. Since then, our understanding has advanced considerably. And, outgrowths of protein folding include the commercial development of new computers, such as IBM’s Blue Gene; new modes of citizen science, including Folding@Home and Foldit; the development of communal scientific competitions, such as CASP; a database of now more than 80,000 protein structures; the Moore’s-Law advancement in biomolecular simulation forcefields; new areas of materials science based on foldable polymers; and a foundation for understanding whole new classes of diseases—such as Alzheimer’s, Parkinson’s, and type II diabetes, called folding diseases—that were not even known when the protein-folding problem was first identified.

In times when there are pressures on science budgets for immediate payoffs, it is worth repeating the well-worn point that untargeted basic science often pays off in unexpected ways.