• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of prosciprotein sciencecshl presssubscriptionsetoc alertsthe protein societyjournal home
Protein Sci. Mar 1995; 4(3): 521–533.
PMCID: PMC2143072

Transmembrane helices predicted at 95% accuracy.


We describe a neural network system that predicts the locations of transmembrane helices in integral membrane proteins. By using evolutionary information as input to the network system, the method significantly improved on a previously published neural network prediction method that had been based on single sequence information. The input data were derived from multiple alignments for each position in a window of 13 adjacent residues: amino acid frequency, conservation weights, number of insertions and deletions, and position of the window with respect to the ends of the protein chain. Additional input was the amino acid composition and length of the whole protein. A rigorous cross-validation test on 69 proteins with experimentally determined locations of transmembrane segments yielded an overall two-state per-residue accuracy of 95%. About 94% of all segments were predicted correctly. When applied to known globular proteins as a negative control, the network system incorrectly predicted fewer than 5% of globular proteins as having transmembrane helices. The method was applied to all 269 open reading frames from the complete yeast VIII chromosome. For 59 of these, at least two transmembrane helices were predicted. Thus, the prediction is that about one-fourth of all proteins from yeast VIII contain one transmembrane helix, and some 20%, more than one.

Full Text

The Full Text of this article is available as a PDF (1.8M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Argos P, Rao JK, Hargrave PA. Structural prediction of membrane-bound proteins. Eur J Biochem. 1982 Nov 15;128(2-3):565–575. [PubMed]
  • Bairoch A, Boeckmann B. The SWISS-PROT protein sequence data bank: current status. Nucleic Acids Res. 1994 Sep;22(17):3578–3580. [PMC free article] [PubMed]
  • Baldwin JM. The probable arrangement of the helices in G protein-coupled receptors. EMBO J. 1993 Apr;12(4):1693–1703. [PMC free article] [PubMed]
  • Bernstein FC, Koetzle TF, Williams GJ, Meyer EF, Jr, Brice MD, Rodgers JR, 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. [PubMed]
  • Cornette JL, Cease KB, Margalit H, Spouge JL, Berzofsky JA, DeLisi C. Hydrophobicity scales and computational techniques for detecting amphipathic structures in proteins. J Mol Biol. 1987 Jun 5;195(3):659–685. [PubMed]
  • Cowan SW, Rosenbusch JP. Folding pattern diversity of integral membrane proteins. Science. 1994 May 13;264(5161):914–916. [PubMed]
  • Edelman J. Quadratic minimization of predictors for protein secondary structure. Application to transmembrane alpha-helices. J Mol Biol. 1993 Jul 5;232(1):165–191. [PubMed]
  • Eisenberg D, Schwarz E, Komaromy M, Wall R. Analysis of membrane and surface protein sequences with the hydrophobic moment plot. J Mol Biol. 1984 Oct 15;179(1):125–142. [PubMed]
  • Eisenberg D, Weiss RM, Terwilliger TC. The hydrophobic moment detects periodicity in protein hydrophobicity. Proc Natl Acad Sci U S A. 1984 Jan;81(1):140–144. [PMC free article] [PubMed]
  • Engelman DM, Steitz TA, Goldman A. Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins. Annu Rev Biophys Biophys Chem. 1986;15:321–353. [PubMed]
  • Fariselli P, Compiani M, Casadio R. Predicting secondary structures of membrane proteins with neural networks. Eur Biophys J. 1993;22(1):41–51. [PubMed]
  • Henderson R, Baldwin JM, Ceska TA, Zemlin F, Beckmann E, Downing KH. Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy. J Mol Biol. 1990 Jun 20;213(4):899–929. [PubMed]
  • Johnston M, Andrews S, Brinkman R, Cooper J, Ding H, Dover J, Du Z, Favello A, Fulton L, Gattung S, et al. Complete nucleotide sequence of Saccharomyces cerevisiae chromosome VIII. Science. 1994 Sep 30;265(5181):2077–2082. [PubMed]
  • Jones DT, Taylor WR, Thornton JM. The rapid generation of mutation data matrices from protein sequences. Comput Appl Biosci. 1992 Jun;8(3):275–282. [PubMed]
  • Kabsch W, Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983 Dec;22(12):2577–2637. [PubMed]
  • Lattman EE. Protein crystallography for all. Proteins. 1994 Feb;18(2):103–106. [PubMed]
  • Manoil C, Beckwith J. A genetic approach to analyzing membrane protein topology. Science. 1986 Sep 26;233(4771):1403–1408. [PubMed]
  • Matthews BW. Comparison of the predicted and observed secondary structure of T4 phage lysozyme. Biochim Biophys Acta. 1975 Oct 20;405(2):442–451. [PubMed]
  • Nakashima H, Nishikawa K. The amino acid composition is different between the cytoplasmic and extracellular sides in membrane proteins. FEBS Lett. 1992 Jun 1;303(2-3):141–146. [PubMed]
  • O'Hara PJ, Sheppard PO, Thøgersen H, Venezia D, Haldeman BA, McGrane V, Houamed KM, Thomsen C, Gilbert TL, Mulvihill ER. The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins. Neuron. 1993 Jul;11(1):41–52. [PubMed]
  • Pearson WR, Lipman DJ. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. [PMC free article] [PubMed]
  • Pearson WR, Miller W. Dynamic programming algorithms for biological sequence comparison. Methods Enzymol. 1992;210:575–601. [PubMed]
  • Persson B, Argos P. Prediction of transmembrane segments in proteins utilising multiple sequence alignments. J Mol Biol. 1994 Mar 25;237(2):182–192. [PubMed]
  • Rost B, Sander C. Improved prediction of protein secondary structure by use of sequence profiles and neural networks. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7558–7562. [PMC free article] [PubMed]
  • Rost B, Sander C. Combining evolutionary information and neural networks to predict protein secondary structure. Proteins. 1994 May;19(1):55–72. [PubMed]
  • Rost B, Sander C. Conservation and prediction of solvent accessibility in protein families. Proteins. 1994 Nov;20(3):216–226. [PubMed]
  • Rost B, Schneider R, Sander C. Progress in protein structure prediction? Trends Biochem Sci. 1993 Apr;18(4):120–123. [PubMed]
  • Rost B, Sander C, Schneider R. Redefining the goals of protein secondary structure prediction. J Mol Biol. 1994 Jan 7;235(1):13–26. [PubMed]
  • Sander C, Schneider R. Database of homology-derived protein structures and the structural meaning of sequence alignment. Proteins. 1991;9(1):56–68. [PubMed]
  • Sander C, Schneider R. The HSSP database of protein structure-sequence alignments. Nucleic Acids Res. 1994 Sep;22(17):3597–3599. [PMC free article] [PubMed]
  • Sipos L, von Heijne G. Predicting the topology of eukaryotic membrane proteins. Eur J Biochem. 1993 May 1;213(3):1333–1340. [PubMed]
  • von Heijne G. Membrane proteins: the amino acid composition of membrane-penetrating segments. Eur J Biochem. 1981 Nov;120(2):275–278. [PubMed]
  • von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. [PMC free article] [PubMed]
  • von Heijne G. Computer analysis of DNA and protein sequences. Eur J Biochem. 1991 Jul 15;199(2):253–256. [PubMed]
  • von Heijne G. Membrane protein structure prediction. Hydrophobicity analysis and the positive-inside rule. J Mol Biol. 1992 May 20;225(2):487–494. [PubMed]
  • von Heijne G, Gavel Y. Topogenic signals in integral membrane proteins. Eur J Biochem. 1988 Jul 1;174(4):671–678. [PubMed]
  • Wang DN, Kühlbrandt W, Sarabia VE, Reithmeier RA. Two-dimensional structure of the membrane domain of human band 3, the anion transport protein of the erythrocyte membrane. EMBO J. 1993 Jun;12(6):2233–2239. [PMC free article] [PubMed]
  • Weiss MS, Schulz GE. Structure of porin refined at 1.8 A resolution. J Mol Biol. 1992 Sep 20;227(2):493–509. [PubMed]

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


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...