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Protein Science : A Publication of the Protein Society logo

Hydrophobic folding units derived from dissimilar monomer structures and their interactions.

C J Tsai1,R Nussinov1
1Laboratory of Mathematical Biology, NCI-FCRDC, Frederick, Maryland 21702, USA.
PMCID: PMC2143523  PMID:9007974

Abstract

We have designed an automated procedure to cut a protein into compact hydrophobic folding units. The hydrophobic units are large enough to contain tertiary non-local interactions, reflecting potential nucleation sites during protein folding. The quality of a hydrophobic folding unit is evaluated by four criteria. The first two correspond to visual characterization of a structural domain, namely, compactness and extent of isolation. We use the definition of Zehfus and Rose (Zehfus MH, Rose GD, 1986, Biochemistry 25:35-340) to calculate the compactness of a cut protein unit. The isolation of a unit is based on the solvent accessible surface area (ASA) originally buried in the interior and exposed to the solvent after cutting. The third quantity is the hydrophobicity, equivalent to the fraction of the buried non-polar ASA with respect to the total non-polar ASA. The last criterion in the evaluation of a folding unit is the number of segments it includes. To conform with the rationale of obtaining hydrophobic units, which may relate to early folding events, the hydrophobic interactions are implicitly and explicitly applied in their generation and assessment. We follow Holm and Sander (Holm L, Sander C, 1994, Proteins 19:256-268) to reduce the multiple cutting-point problem to a one-dimensional search for all reasonable trial cuts. However, as here we focus on the hydrophobic cores, the contact matrix used to obtain the first non-trivial eigenvector contains only hydrophobic contracts, rather than all, hydrophobic and hydrophilic, interactions. This dataset of hydrophobic folding units, derived from structurally dissimilar single chain monomers, is particularly useful for investigations of the mechanism of protein folding. For cases where there are kinetic data, the one or more hydrophobic folding units generated for a protein correlate with the two or with the three-state folding process observed. We carry out extensive amino acid sequence order independent structural comparisons to generate a structurally non-redundant set of hydrophobic folding units for fold recognition and for statistical purposes.

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Selected References

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  1. Bennett M. J., Schlunegger M. P., Eisenberg D. 3D domain swapping: a mechanism for oligomer assembly. Protein Sci. 1995 Dec;4(12):2455–2468. doi: 10.1002/pro.5560041202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Crippen G. M. The tree structural organization of proteins. J Mol Biol. 1978 Dec 15;126(3):315–332. doi: 10.1016/0022-2836(78)90043-8. [DOI] [PubMed] [Google Scholar]
  3. Dill K. A. Dominant forces in protein folding. Biochemistry. 1990 Aug 7;29(31):7133–7155. doi: 10.1021/bi00483a001. [DOI] [PubMed] [Google Scholar]
  4. Fersht A. R. Characterizing transition states in protein folding: an essential step in the puzzle. Curr Opin Struct Biol. 1995 Feb;5(1):79–84. doi: 10.1016/0959-440x(95)80012-p. [DOI] [PubMed] [Google Scholar]
  5. Fersht A. R. Optimization of rates of protein folding: the nucleation-condensation mechanism and its implications. Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):10869–10873. doi: 10.1073/pnas.92.24.10869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fischer D., Wolfson H., Lin S. L., Nussinov R. Three-dimensional, sequence order-independent structural comparison of a serine protease against the crystallographic database reveals active site similarities: potential implications to evolution and to protein folding. Protein Sci. 1994 May;3(5):769–778. doi: 10.1002/pro.5560030506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Freire E. Thermodynamics of partly folded intermediates in proteins. Annu Rev Biophys Biomol Struct. 1995;24:141–165. doi: 10.1146/annurev.bb.24.060195.001041. [DOI] [PubMed] [Google Scholar]
  8. Griko Y. V., Makhatadze G. I., Privalov P. L., Hartley R. W. Thermodynamics of barnase unfolding. Protein Sci. 1994 Apr;3(4):669–676. doi: 10.1002/pro.5560030414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Holm L., Sander C. Parser for protein folding units. Proteins. 1994 Jul;19(3):256–268. doi: 10.1002/prot.340190309. [DOI] [PubMed] [Google Scholar]
  10. Murphy K. P., Bhakuni V., Xie D., Freire E. Molecular basis of co-operativity in protein folding. III. Structural identification of cooperative folding units and folding intermediates. J Mol Biol. 1992 Sep 5;227(1):293–306. doi: 10.1016/0022-2836(92)90699-k. [DOI] [PubMed] [Google Scholar]
  11. Naor D., Fischer D., Jernigan R. L., Wolfson H. J., Nussinov R. Amino acid pair interchanges at spatially conserved locations. J Mol Biol. 1996 Mar 15;256(5):924–938. doi: 10.1006/jmbi.1996.0138. [DOI] [PubMed] [Google Scholar]
  12. Noguti T., Sakakibara H., Go M. Localization of hydrogen-bonds within modules in barnase. Proteins. 1993 Aug;16(4):357–363. doi: 10.1002/prot.340160405. [DOI] [PubMed] [Google Scholar]
  13. Nussinov R., Wolfson H. J. Efficient detection of three-dimensional structural motifs in biological macromolecules by computer vision techniques. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10495–10499. doi: 10.1073/pnas.88.23.10495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Otzen D. E., Itzhaki L. S., elMasry N. F., Jackson S. E., Fersht A. R. Structure of the transition state for the folding/unfolding of the barley chymotrypsin inhibitor 2 and its implications for mechanisms of protein folding. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10422–10425. doi: 10.1073/pnas.91.22.10422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Privalov P. L. Intermediate states in protein folding. J Mol Biol. 1996 May 24;258(5):707–725. doi: 10.1006/jmbi.1996.0280. [DOI] [PubMed] [Google Scholar]
  16. Rashin A. A. Location of domains in globular proteins. Nature. 1981 May 7;291(5810):85–87. doi: 10.1038/291085a0. [DOI] [PubMed] [Google Scholar]
  17. Rose G. D. Hierarchic organization of domains in globular proteins. J Mol Biol. 1979 Nov 5;134(3):447–470. doi: 10.1016/0022-2836(79)90363-2. [DOI] [PubMed] [Google Scholar]
  18. Shakhnovich E., Abkevich V., Ptitsyn O. Conserved residues and the mechanism of protein folding. Nature. 1996 Jan 4;379(6560):96–98. doi: 10.1038/379096a0. [DOI] [PubMed] [Google Scholar]
  19. Shrake A., Rupley J. A. Environment and exposure to solvent of protein atoms. Lysozyme and insulin. J Mol Biol. 1973 Sep 15;79(2):351–371. doi: 10.1016/0022-2836(73)90011-9. [DOI] [PubMed] [Google Scholar]
  20. Siddiqui A. S., Barton G. J. Continuous and discontinuous domains: an algorithm for the automatic generation of reliable protein domain definitions. Protein Sci. 1995 May;4(5):872–884. doi: 10.1002/pro.5560040507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sowdhamini R., Blundell T. L. An automatic method involving cluster analysis of secondary structures for the identification of domains in proteins. Protein Sci. 1995 Mar;4(3):506–520. doi: 10.1002/pro.5560040317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Struthers M. D., Cheng R. P., Imperiali B. Design of a monomeric 23-residue polypeptide with defined tertiary structure. Science. 1996 Jan 19;271(5247):342–345. doi: 10.1126/science.271.5247.342. [DOI] [PubMed] [Google Scholar]
  23. Swindells M. B. A procedure for detecting structural domains in proteins. Protein Sci. 1995 Jan;4(1):103–112. doi: 10.1002/pro.5560040113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tsai C. J., Lin S. L., Wolfson H. J., Nussinov R. A dataset of protein-protein interfaces generated with a sequence-order-independent comparison technique. J Mol Biol. 1996 Jul 26;260(4):604–620. doi: 10.1006/jmbi.1996.0424. [DOI] [PubMed] [Google Scholar]
  25. Tsai C. J., Lin S. L., Wolfson H. J., Nussinov R. Studies of protein-protein interfaces: a statistical analysis of the hydrophobic effect. Protein Sci. 1997 Jan;6(1):53–64. doi: 10.1002/pro.5560060106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wodak S. J., Janin J. Location of structural domains in protein. Biochemistry. 1981 Nov 10;20(23):6544–6552. doi: 10.1021/bi00526a005. [DOI] [PubMed] [Google Scholar]
  27. Zehfus M. H. Binary discontinuous compact protein domains. Protein Eng. 1994 Mar;7(3):335–340. doi: 10.1093/protein/7.3.335. [DOI] [PubMed] [Google Scholar]
  28. Zehfus M. H. Improved calculations of compactness and a reevaluation of continuous compact units. Proteins. 1993 Jul;16(3):293–300. doi: 10.1002/prot.340160307. [DOI] [PubMed] [Google Scholar]
  29. Zehfus M. H., Rose G. D. Compact units in proteins. Biochemistry. 1986 Sep 23;25(19):5759–5765. doi: 10.1021/bi00367a062. [DOI] [PubMed] [Google Scholar]

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