Prediction of probable pathways of folding in globular proteins

A method is described for the prediction of probable folding pathways of globular proteins, based on the analysis of distance maps. It is applicable to proteins of unknown spatial structure but known amino acid sequence as well as to proteins of known structure. It is based on an objective procedure for the determination of the boundary of compact regions that contain high densities of interresidue contacts on the distance map of a globular protein. The procedure can be used both with contact maps derived from a known three-dimensional protein structure and with predicted contact maps computed by means of a statistical procedure from the amino acid sequence alone. The computed contact map can also be used to predict the location of compact short-range structures, viz. α-helices and β-turns, thereby complementing other statistical predictive procedures. The method provides an objective basis for the derivation of a theoretically predicted pathway of protein folding, proposed by us earlier [Tanaka and Scheraga (1977) Macromolecules10, 291–304; Némethy and Scheraga (1979) Proc. Natl. Acad. Sci., U.S.A.76, 6050–6054].

[1]  H. Scheraga,et al.  Analysis of Conformations of Amino Acid Residues and Prediction of Backbone Topography in Proteins , 1974 .

[2]  M. Desmadril,et al.  Existence of intermediates in the refolding of T4 lysozyme at pH 7.4. , 1981, Biochemical and biophysical research communications.

[3]  H A Scheraga,et al.  A possible folding pathway of bovine pancreatic RNase. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[4]  J. Richardson,et al.  Determination and analysis of the 2 A-structure of copper, zinc superoxide dismutase. , 1980, Journal of molecular biology.

[5]  J. Garnier,et al.  Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. , 1978, Journal of molecular biology.

[6]  G J Williams,et al.  The Protein Data Bank: a computer-based archival file for macromolecular structures. , 1977, Journal of molecular biology.

[7]  L. Delbaere,et al.  The 2.8 A resolution structure of Streptomyces griseus protease B and its homology with alpha-chymotrypsin and Streptomyces griseus protease A. , 1979, Canadian Journal of Biochemistry.

[8]  D. F. Koenig,et al.  Structure of Hen Egg-White Lysozyme: A Three-dimensional Fourier Synthesis at 2 Å Resolution , 1965, Nature.

[9]  B. Matthews,et al.  Structure of the lysozyme from bacteriophage T4: an electron density map at 2.4 A resolution. , 1978, Journal of molecular biology.

[10]  P. Y. Chou,et al.  Empirical predictions of protein conformation. , 1978, Annual review of biochemistry.

[11]  H. Scheraga,et al.  Status of empirical methods for the prediction of protein backbone topography. , 1976, Biochemistry.

[12]  Takeshi Kikuchi,et al.  Prediction of the packing arrangement of strands in β-sheets of globular proteins , 1988, Journal of protein chemistry.

[13]  P. Y. Chou,et al.  Prediction of protein conformation. , 1974, Biochemistry.

[14]  J. Drenth,et al.  The structure of papain. , 1971, Advances in protein chemistry.

[15]  H A Scheraga,et al.  Improvements in the prediction of protein backbone topography by reduction of statistical errors. , 1979, Biochemistry.

[16]  M. Desmadril,et al.  Evidence for intermediates during unfolding and refolding of a two-domain protein, phage T4 lysozyme: equilibrium and kinetic studies. , 1984, Biochemistry.

[17]  H. Watson,et al.  The Stereochemistry of the Protein Myoglobin , 1976 .

[18]  H. Scheraga,et al.  Model of protein folding: inclusion of short-, medium-, and long-range interactions. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[19]  A. W. Hanson,et al.  The three-dimensional structure of ribonuclease-S. Interpretation of an electron density map at a nominal resolution of 2 A. , 1970, The Journal of biological chemistry.

[20]  H. Scheraga,et al.  Hypothesis about the mechanism of protein folding. , 1977, Macromolecules.

[21]  H. Scheraga,et al.  Prediction of the location of structural domains in globular proteins , 1988, Journal of protein chemistry.

[22]  G. Schulz,et al.  Three-dimensional structure of adenyl kinase , 1974, Nature.