Stony Brook Researchers Look Back on Scientific Advances Made as a Result of a 50-Year Old Puzzle
Effort to solve questions on protein folding created field of protein physical science that has led to major scientific advances
STONY BROOK, N.Y., Nov. 22, 2012 – Fifty years after scientists first posed a question about protein folding, the search for answers has led to the creation of a full-fledged field of research that led to major advances in supercomputers, new materials and drug discovery, and shaped our understanding of the basic processes of life, including so-called "protein-folding diseases" such as Alzheimer's, Parkinson's and type II diabetes.
In a review article published in the Nov. 23, 2012 issue of the journal Science, Stony Brook University researchers reviewed the progress on a 50-year-old puzzle called the Protein Folding Problem. Ken Dill and Justin MacCallum of Stony Brook’s Louis and Beatrice Laufer Center for Physical and Quantitative Biology show how a community of scientific researchers rose to tackle a grand-challenge problem of very basic science that had no obvious payoff at the time.
“Protein folding is a quintessential basic science. There has been no specific commercial target, yet the collateral payoffs have been broad and deep,” the researchers said in their paper, The Protein Folding Problem, 50 Years On.
This year marks the 50th anniversary of the 1962 Nobel Prize in Chemistry awarded to Max Perutz and John Kendrew for their pioneering work in determining the structure of globular proteins. That work laid the foundation for structural biology, which interprets molecular level biological mechanisms in terms of the structures of proteins and other biomolecules. Their work also raised the question of how protein structures are explained by physical principles.
Since Perutz and Kendrew discovered the structures of two proteins, nearly 80,000 protein structures have been discovered. The protein folding "problem" arose when Perutz and Kendrew were unable to make sense of how the folded structure of the protein molecule was related to its sequence of bead types. Ever since then, there has been great interest in understanding the protein-folding "code": how does a given string of amino acids lead to a particular balled-up ("native") structure of a protein?
The protein folding problem became a set of three inter-related puzzles: What is the folding code? How does the protein find its one native structure in fractions of a second inside the cell (the needle-in-a-haystack problem)? And: Can we make a computer method that can discover new structures of proteins from the large number of amino acid sequences that are now known?
Dill, Director of the Laufer Center and Distinguished Professor of Physics and Chemistry, and MacCallum, a junior fellow at the Laufer Center, describe how huge advances have been made on all three fronts. They detail some very important collateral payoffs of this work that was completely unanticipated at the time, including the development of the IBM Blue Gene computer and distributed-grid computing, computer-based methods for discovering new pharmaceuticals, a deeper understanding of molecular mechanisms in biology, a deeper understanding of the inter-atomic interactions inside proteins (that has also involved Stony Brook Laufer Center researchers Carlos Simmerling, David Green, and Rob Rizzo), and a new class of very promising polymer materials called "foldamers".
Dill and MacCallum argue that what started out as one compelling question of basic science has now become an entire field of theoretical and experimental approaches in which many questions are now leading to a few answers and many more questions.
Schematic illustration of a protein folding along side its energy landscape. [Credit: C. Fennell, Laufer Junior Fellow]
© Stony Brook University 2012