Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Aug;79(16):5107–5110. doi: 10.1073/pnas.79.16.5107

Calculation of the three-dimensional structure of the membrane-bound portion of melittin from its amino acid sequence.

M R Pincus, R D Klausner, H A Scheraga
PMCID: PMC346840  PMID: 6956920

Abstract

The structure of the NH2-terminal, 20-residue membrane-bound portion of melittin has been computed with empirical energies (ECEPP, Empirical Conformational Energy Program for Peptides). First, a search was made for long stretches of nonpolar residues. Then, the low-energy conformations of these segments were built up by combining successively the low-energy conformations of their component di- and tripeptides. The minimum-energy conformations of each of these component peptides used in this buildup process were selected so that each had a distinct backbone conformation; these distinct backbone conformations were designated as nondegenerate minima. Structured segments (i.e., those with only a few low-energy conformations) resulting from this process were identified and used as nucleation sites for building up larger structures by adding adjacent peptide segments. At each stage, the energy of each structure was minimized. Only two low-energy structures were found, both of which were alpha-helical from Gly-1 to Thr-10 and from Pro-14 to Ile-20. In one of them, the first helix continues through Thr-11-Gly-12; in the other, there is a bend at Thr-11-Gly-12. However, because of compensating changes in the dihedral angles, both structures are very similar. The calculated structures seem to agree well with experimental data.

Full text

PDF
5107

Selected References

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

  1. Brown L. R., Braun W., Kumar A., Wüthrich K. High resolution nuclear magnetic resonance studies of the conformation and orientation of melittin bound to a lipid-water interface. Biophys J. 1982 Jan;37(1):319–328. doi: 10.1016/S0006-3495(82)84680-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dygert M., Gō N., Scheraga H. A. Use of a symmetry condition to compute the conformation of gramicidin S1. Macromolecules. 1975 Nov-Dec;8(6):750–761. doi: 10.1021/ma60048a016. [DOI] [PubMed] [Google Scholar]
  3. Engelman D. M., Steitz T. A. The spontaneous insertion of proteins into and across membranes: the helical hairpin hypothesis. Cell. 1981 Feb;23(2):411–422. doi: 10.1016/0092-8674(81)90136-7. [DOI] [PubMed] [Google Scholar]
  4. Howard J. C., Ali A., Scheraga H. A., Momany F. A. Investigation of the conformations of four tetrapeptides by nuclear magnetic resonance and circular dichroism spectroscopy, and conformational energy calculations. Macromolecules. 1975 Sep-Oct;8(5):607–622. doi: 10.1021/ma60047a008. [DOI] [PubMed] [Google Scholar]
  5. Meirovitch H., Scheraga H. A. Introduction of short-range restrictions in a protein-folding algorithm involving a long-range geometrical restriction and short-, medium-, and long-range interactions. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6584–6587. doi: 10.1073/pnas.78.11.6584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Pincus M. R., Klausner R. D. Prediction of the three-dimensional structure of the leader sequence of pre-kappa light chain, a hexadecapeptide. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3413–3417. doi: 10.1073/pnas.79.11.3413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ponnuswamy P. K., Warme P. K., Scheraga H. A. Role of medium-range interactions in proteins. Proc Natl Acad Sci U S A. 1973 Mar;70(3):830–833. doi: 10.1073/pnas.70.3.830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Rackovsky S., Scheraga H. A. Intermolecular anti-parallel beta sheet: Comparison of predicted and observed conformations of gramicidin S. Proc Natl Acad Sci U S A. 1980 Dec;77(12):6965–6967. doi: 10.1073/pnas.77.12.6965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Terwilliger T. C., Weissman L., Eisenberg D. The structure of melittin in the form I crystals and its implication for melittin's lytic and surface activities. Biophys J. 1982 Jan;37(1):353–361. doi: 10.1016/S0006-3495(82)84683-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Wako H., Scheraga H. A. Visualization of the nature of protein folding by a study of a distance constraint approach in two-dimensional models. Biopolymers. 1982 Mar;21(3):611–632. doi: 10.1002/bip.360210310. [DOI] [PubMed] [Google Scholar]
  11. Zimmerman S. S., Scheraga H. A. Influence of local interactions on protein structure. I. Conformational energy studies of N-acetyl-N'-methylamides of Pro-X and X-Pro dipeptides. Biopolymers. 1977 Apr;16(4):811–843. doi: 10.1002/bip.1977.360160408. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES