Skip to main content
PMC home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1995 Jan;4(1):93–102. doi: 10.1002/pro.5560040112

A procedure for the automatic determination of hydrophobic cores in protein structures.

M B Swindells 1
PMCID: PMC2142969  PMID: 7773181

Abstract

An algorithm is described for automatically detecting hydrophobic cores in proteins of known structure. Three pieces of information are considered in order to achieve this goal. These are: secondary structure, side-chain accessibility, and side-chain-side-chain contacts. Residues are considered to contribute to a core when they occur in regular secondary structure and have buried side chains that form predominantly nonpolar contacts with one another. This paper describes the algorithm's application to families of proteins with conserved topologies but low sequence similarities. The aim of this investigation is to determine the efficacy of the algorithm as well as to study the extent to which similar cores are identified within a common topology.

Full Text

The Full Text of this article is available as a PDF (8.6 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bashford D., Chothia C., Lesk A. M. Determinants of a protein fold. Unique features of the globin amino acid sequences. J Mol Biol. 1987 Jul 5;196(1):199–216. doi: 10.1016/0022-2836(87)90521-3. [DOI] [PubMed] [Google Scholar]
  2. Beamer L. J., Pabo C. O. Refined 1.8 A crystal structure of the lambda repressor-operator complex. J Mol Biol. 1992 Sep 5;227(1):177–196. doi: 10.1016/0022-2836(92)90690-l. [DOI] [PubMed] [Google Scholar]
  3. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  4. Bowie J. U., Lüthy R., Eisenberg D. A method to identify protein sequences that fold into a known three-dimensional structure. Science. 1991 Jul 12;253(5016):164–170. doi: 10.1126/science.1853201. [DOI] [PubMed] [Google Scholar]
  5. Chothia C., Lesk A. M. Evolution of proteins formed by beta-sheets. I. Plastocyanin and azurin. J Mol Biol. 1982 Sep 15;160(2):309–323. doi: 10.1016/0022-2836(82)90178-4. [DOI] [PubMed] [Google Scholar]
  6. Fermi G., Perutz M. F., Shaanan B., Fourme R. The crystal structure of human deoxyhaemoglobin at 1.74 A resolution. J Mol Biol. 1984 May 15;175(2):159–174. doi: 10.1016/0022-2836(84)90472-8. [DOI] [PubMed] [Google Scholar]
  7. Finzel B. C., Clancy L. L., Holland D. R., Muchmore S. W., Watenpaugh K. D., Einspahr H. M. Crystal structure of recombinant human interleukin-1 beta at 2.0 A resolution. J Mol Biol. 1989 Oct 20;209(4):779–791. doi: 10.1016/0022-2836(89)90606-2. [DOI] [PubMed] [Google Scholar]
  8. Holm L., Sander C. Protein structure comparison by alignment of distance matrices. J Mol Biol. 1993 Sep 5;233(1):123–138. doi: 10.1006/jmbi.1993.1489. [DOI] [PubMed] [Google Scholar]
  9. Holmes M. A., Stenkamp R. E. Structures of met and azidomet hemerythrin at 1.66 A resolution. J Mol Biol. 1991 Aug 5;220(3):723–737. doi: 10.1016/0022-2836(91)90113-k. [DOI] [PubMed] [Google Scholar]
  10. Hubbard T. J., Blundell T. L. Comparison of solvent-inaccessible cores of homologous proteins: definitions useful for protein modelling. Protein Eng. 1987 Jun;1(3):159–171. doi: 10.1093/protein/1.3.159. [DOI] [PubMed] [Google Scholar]
  11. Jones D. T., Taylor W. R., Thornton J. M. A new approach to protein fold recognition. Nature. 1992 Jul 2;358(6381):86–89. doi: 10.1038/358086a0. [DOI] [PubMed] [Google Scholar]
  12. Kabsch W., Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983 Dec;22(12):2577–2637. doi: 10.1002/bip.360221211. [DOI] [PubMed] [Google Scholar]
  13. Lederer F., Glatigny A., Bethge P. H., Bellamy H. D., Matthew F. S. Improvement of the 2.5 A resolution model of cytochrome b562 by redetermining the primary structure and using molecular graphics. J Mol Biol. 1981 Jun 5;148(4):427–448. doi: 10.1016/0022-2836(81)90185-6. [DOI] [PubMed] [Google Scholar]
  14. Lee B., Richards F. M. The interpretation of protein structures: estimation of static accessibility. J Mol Biol. 1971 Feb 14;55(3):379–400. doi: 10.1016/0022-2836(71)90324-x. [DOI] [PubMed] [Google Scholar]
  15. Lesk A. M., Chothia C. Evolution of proteins formed by beta-sheets. II. The core of the immunoglobulin domains. J Mol Biol. 1982 Sep 15;160(2):325–342. doi: 10.1016/0022-2836(82)90179-6. [DOI] [PubMed] [Google Scholar]
  16. Lesk A. M., Chothia C. How different amino acid sequences determine similar protein structures: the structure and evolutionary dynamics of the globins. J Mol Biol. 1980 Jan 25;136(3):225–270. doi: 10.1016/0022-2836(80)90373-3. [DOI] [PubMed] [Google Scholar]
  17. Miller S., Janin J., Lesk A. M., Chothia C. Interior and surface of monomeric proteins. J Mol Biol. 1987 Aug 5;196(3):641–656. doi: 10.1016/0022-2836(87)90038-6. [DOI] [PubMed] [Google Scholar]
  18. Morris A. L., MacArthur M. W., Hutchinson E. G., Thornton J. M. Stereochemical quality of protein structure coordinates. Proteins. 1992 Apr;12(4):345–364. doi: 10.1002/prot.340120407. [DOI] [PubMed] [Google Scholar]
  19. Murzin A. G., Lesk A. M., Chothia C. beta-Trefoil fold. Patterns of structure and sequence in the Kunitz inhibitors interleukins-1 beta and 1 alpha and fibroblast growth factors. J Mol Biol. 1992 Jan 20;223(2):531–543. doi: 10.1016/0022-2836(92)90668-a. [DOI] [PubMed] [Google Scholar]
  20. Onesti S., Brick P., Blow D. M. Crystal structure of a Kunitz-type trypsin inhibitor from Erythrina caffra seeds. J Mol Biol. 1991 Jan 5;217(1):153–176. doi: 10.1016/0022-2836(91)90618-g. [DOI] [PubMed] [Google Scholar]
  21. Orengo C. A., Flores T. P., Taylor W. R., Thornton J. M. Identification and classification of protein fold families. Protein Eng. 1993 Jul;6(5):485–500. doi: 10.1093/protein/6.5.485. [DOI] [PubMed] [Google Scholar]
  22. Phillips S. E., Schoenborn B. P. Neutron diffraction reveals oxygen-histidine hydrogen bond in oxymyoglobin. Nature. 1981 Jul 2;292(5818):81–82. doi: 10.1038/292081a0. [DOI] [PubMed] [Google Scholar]
  23. Richards F. M., Kundrot C. E. Identification of structural motifs from protein coordinate data: secondary structure and first-level supersecondary structure. Proteins. 1988;3(2):71–84. doi: 10.1002/prot.340030202. [DOI] [PubMed] [Google Scholar]
  24. Ryu S. E., Kwong P. D., Truneh A., Porter T. G., Arthos J., Rosenberg M., Dai X. P., Xuong N. H., Axel R., Sweet R. W. Crystal structure of an HIV-binding recombinant fragment of human CD4. Nature. 1990 Nov 29;348(6300):419–426. doi: 10.1038/348419a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Umezawa Y., Umeyama H. Computer screening and visualization of hydrophobic core of protein. Chem Pharm Bull (Tokyo) 1988 Dec;36(12):4652–4658. doi: 10.1248/cpb.36.4652. [DOI] [PubMed] [Google Scholar]
  27. Wlodawer A., Nachman J., Gilliland G. L., Gallagher W., Woodward C. Structure of form III crystals of bovine pancreatic trypsin inhibitor. J Mol Biol. 1987 Dec 5;198(3):469–480. doi: 10.1016/0022-2836(87)90294-4. [DOI] [PubMed] [Google Scholar]
  28. Zhang J. D., Cousens L. S., Barr P. J., Sprang S. R. Three-dimensional structure of human basic fibroblast growth factor, a structural homolog of interleukin 1 beta. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3446–3450. doi: 10.1073/pnas.88.8.3446. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES