• DOI:10.1126/science.1219021
• Corpus ID: 5756068

The Protein-Folding Problem, 50 Years On

@article{Dill2012ThePP,
  title={The Protein-Folding Problem, 50 Years On},
  author={Ken A. Dill and Justin L. MacCallum},
  journal={Science},
  year={2012},
  volume={338},
  pages={1042 - 1046}
}

• K. Dill, J. MacCallum
• Published 23 November 2012
• Physics, Medicine
• Science

Protein Folding: Past and Future Fifty years ago the Nobel Prize in chemistry was awarded to Max Perutz and John Kendrew for determining the structure of globular proteins. Since first viewing their structure of myoglobin, scientists have sought to understand protein folding. Dill and MacCallum (p. 1042) review the progress that has been made on three central questions: What is the code that relates sequence to structure? How do proteins fold so fast? Can protein structure be computationally predicted? While we have come some way toward answering these questions, new questions have been gene rated. It is no longer useful to talk about “solving the protein-folding problem”—protein folding has grown into a field of research where the next 50 years promise to be as exciting as the last. The protein-folding problem was first posed about one half-century ago. The term refers to three broad questions: (i) What is the physical code by which an amino acid sequence dictates a protein’s native structure? (ii) How can proteins fold so fast? (iii) Can we devise a computer algorithm to predict protein structures from their sequences? We review progress on these problems. In a few cases, computer simulations of the physical forces in chemically detailed models have now achieved the accurate folding of small proteins. We have learned that proteins fold rapidly because random thermal motions cause conformational changes leading energetically downhill toward the native structure, a principle that is captured in funnel-shaped energy landscapes. And thanks in part to the large Protein Data Bank of known structures, predicting protein structures is now far more successful than was thought possible in the early days. What began as three questions of basic science one half-century ago has now grown into the full-fledged research field of protein physical science.