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The Protein Folding Problem

FEB 01, 1993
Understanding and predicting the three‐dimensional structures of proteins from their sequences of amino acids requires both basic knowledge of molecular forces and sophisticated computer programs that search for the correct configurations.
Hue Sun Chan
Ken A. Dill

Thousands of different types of proteins occur in biological organisms. They are responsible for catalyzing and regulating biochemical reactions, transporting molecules, the chemistry of vision and of the photosynthetic conversion of light to growth, and they form the basis of structures such as skin, hair and tendon. Protein molecules have remarkable structures. A protein is a linear chain of a particular sequence of monomer units. A major class of proteins, globular proteins, ball up into compact configurations that can have much internal symmetry. (See figure 1.) Each globular protein has a unique folded state, determined by its sequence of monomers.

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References

  1. 1. J. S. Richardson, Adv. Protein Chem. 34, 167 (1981). https://doi.org/APCHA2
    C. Branden, J. Tooze, Introduction to Protein Structure, Garland, New York (1991).

  2. 2. W. R. Taylor, ed., Patterns in Protein Sequence and Structure, Springer‐Verlag, New York (1992).

  3. 3. D. G. Kneller, F. E. Cohen, R. Langridge, J. Mol. Biol. 214, 171 (1990). https://doi.org/JMOBAK
    H. Bohr, J. Bohr, S. Brunak, R. M. J. Cotterill, H. Fredholm, B. Lautrup, S. B. Petersen, FEBS Lett. 261, 43 (1990). https://doi.org/FEBLAL
    M. S. Friedrichs, R. A. Goldstein, P. G. Wolynes, J. Mol. Biol. 222, 1013 (1991), https://doi.org/JMOBAK
    and refs. therein.R. Goldstein, Z. A. Luthey‐Schulten, P. G. Wolynes, Proc. Natl. Acad. Sci. USA 89, 4918, 9029 (1992).

  4. 4. C. Levinthal, J. Chim. Phys. 65, 44 (1968).https://doi.org/PNASA6

  5. 5. J. A. McCammon, S. C. Harvey, Dynamics of Proteins and Nucleic Acids, Cambridge U.P., New York (1989), and refs. therein.

  6. 6. A. E. Mirsky, L. Pauling, Proc. Natl. Acad. Sci. USA 22, 439 (1936).https://doi.org/PNASA6

  7. 7. L. Pauling, R. B. Corey, H. R. Branson, Proc. Natl. Acad. Sci. USA 37, 205 (1951). https://doi.org/PNASA6
    L. Pauling, R. B. Corey, Proc. Natl. Acad. Sci. USA 37, 235, 251272, 729 (1951).

  8. 8. W. Kauzmann, Adv. Protein Chem. 14, 1 (1959).

  9. 9. K. A. Dill, Biochemistry 29, 7133 (1990).https://doi.org/BICHAW

  10. 10. H. S. Chan, K. A. Dill, Annu. Rev. Biophys. Biophys. Chem. 20, 447 (1991).https://doi.org/ARBCEY

  11. 11. P. J. Flory, Principles of Polymer Chemistry, Cornell U.P., Ithaca, N.Y. (1953).
    O. B. Ptitsyn, A. K. Kron, Yu. Ye. Eizner, J. Polymer Sci. C 16, 3509 (1968).
    P.‐G. de Gennes, J. Phys. Lett. (Paris) 36, L55 (1975). https://doi.org/JPSLBO
    C. B. Post, B. H. Zimm, Biopolymers 18, 1487 (1979). https://doi.org/BIPMAA
    I. C. Sanchez, Macromolecules 12, 980 (1979).https://doi.org/MAMOBX

  12. 12. S. F. Edwards, Proc. Phys. Soc. London 85, 613 (1965). https://doi.org/PPSOAU
    I. M. Lifshitz, A. Yu. Grosberg,A. R. Khokhlov, Rev. Mod. Phys. 50, 683 (1978). https://doi.org/RMPHAT
    A. Yu. Grosberg, D. V. Kuznetsov, Vysokomolek. Soed. 26B, 701, 706 (1984).
    A. Yu. Grosberg, A. R. Khokhlov, Sov. Sci. Rev. A 8, 147 (1987).

  13. 13. K. A. Dill, Biochemistry 24, 1501 (1985). https://doi.org/BICHAW
    D. O. V. Alonso, K. A. Dill, D. Stigter, Biopolymers 31, 1631 (1991).https://doi.org/BIPMAA

  14. 14. B. Derrida, Phys. Rev. B 24, 2613 (1981). https://doi.org/PRBMDO
    J. D. Bryngelson, P. G. Wolynes, Proc. Natl. Acad. Sci. USA 84, 7524 (1987); https://doi.org/PNASA6
    J. D. Bryngelson, P. G. Wolynes, J. Phys. Chem. 93, 6902 (1989); https://doi.org/JPCHAX
    J. D. Bryngelson, P. G. Wolynes, Biopolymers 30, 177 (1990). https://doi.org/BIPMAA
    T. Garel, H. Orland, Europhys. Lett. 6, 307, 597 (1988). https://doi.org/EULEEJ
    E. I. Shakhnovich, A. M. Gutin, Biophys. Chem. 34, 187 (1989).https://doi.org/BICIAZ

  15. 15. P. G. Wolynes, in Biologically Inspired Physics, L. Peliti, ed., Plenum, New York (1991), p. 15.
    E. Shakhnovich, G. Farztdinov, A. M. Gutin, M. Karplus, Phys. Rev. Lett. 67, 1665 (1991). https://doi.org/PRLTAO
    P. E. Leopold, M. Montal, J. N. Onuchic, Proc. Natl. Acad. Sci. USA 89, 8721 (1992).https://doi.org/PNASA6

  16. 16. W. J. C. Orr, Trans. Faraday Soc. 43, 12 (1947). https://doi.org/TFSOA4
    W. J. C. Orr, C. Domb.Adv. Chem. Phys. 15, 229 (1969), and refs. therein.

  17. 17. K. F. Lau, K. A. Dill, Macromolecules 22, 3986 (1989); https://doi.org/MAMOBX
    K. F. Lau, K. A. Dill, Proc. Natl. Acad. Sci. USA 87, 638 (1990). https://doi.org/PNASA6
    H. S. Chan, K. A. Dill, J. Chem. Phys. 95, 3775 (1991). https://doi.org/JCPSA6
    D. J. Lipman, W. J. Wilbur, Proc. R. Soc. London, Ser. B, 245, 7 (1991).
    D. Shortle, H. S. Chan, K. A. Dill, Protein Sci. 1, 201 (1992). https://doi.org/PRCIEI
    K. Yue, K. A. Dill, Proc. Natl. Acad. Sci. USA 89, 4163 (1992).https://doi.org/PNASA6

  18. 18. See, for example, B. W. Matthews, Biochemistry 26, 6885 (1987); https://doi.org/BICHAW
    W. A. Lim, R. T. Sauer, Nature 339, 31 (1989).https://doi.org/NATUAS

  19. 19. M. Levitt, A. Warshel, Nature 253, 694 (1975). https://doi.org/NATUAS
    J. Skolnick, A. Kolinski, Annu. Rev. Phys. Chem. 40, 207 (1989); https://doi.org/ARPLAP
    J. Skolnick, A. Kolinski, J. Mol. Biol. 221, 499 (1991). https://doi.org/JMOBAK
    J. D. Honeycutt, D. Thirumalai, Proc. Natl. Acad. Sci. USA 87, 3526 (1990); https://doi.org/PNASA6
    J. D. Honeycutt, D. Thirumalai, Biopolymers 32, 695 (1992). https://doi.org/BIPMAA
    S. Sun, “Reduced Representation Model of Protein Structure Prediction: Statistical Potential and Genetic Algorithms,” to appear in Protein Sci.

  20. 20. J. W. Bowie, R. Lüthy, D. Eisenberg, Science 253, 164 (1991). https://doi.org/SCIEAS
    D. T. Jones, W. R. Taylor, J. M. Thornton, Nature 358, 86 (1992).https://doi.org/NATUAS

  21. 21. S. Miyazawa, R. L. Jernigan, Macromolecules 18, 534 (1985). https://doi.org/MAMOBX
    M. J. Sippl, J. Mol. Biol. 213, 859 (1990). https://doi.org/JMOBAK
    D. G. Covell, R. L. Jernigan, Biochemistry 29, 3287 (1990).https://doi.org/BICHAW

  22. 22. L. Piela, J. Kostrowicki, H. A. Scheraga, J. Phys. Chem. 93, 3339 (1989). https://doi.org/JPCHAX
    R. L. Somorjai, J. Phys. Chem. 95, 4141 (1991). https://doi.org/JPCHAX
    T. Head‐Gordon, F. H. Stillinger, J. Arrecis, Proc. Natl. Acad. Sci. USA 88, 11076 (1991).https://doi.org/PNASA6

  23. 23. E. M. O’Toole, A. Z. Panagiotopoulos, J. Chem. Phys. 97, 8644 (1992).https://doi.org/JCPSA6

  24. 24. K. A. Dill, K. M. Fiebig, H. S. Chan, “Cooperativity in Protein Folding Kinetics,” to appear in Proc. Natl. Acad. Sci. USA 90 (1993).
    K. M. Fiebig, K. A. Dill, “Protein Core Assembly Processes,” to appear inJ. Chem. Phys. 98 (1993).

More about the authors

Hue Sun Chan, University of California, San Francisco.

Ken A. Dill, University of California, San Francisco.

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This Content Appeared In
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Volume 46, Number 2

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