Transmembrane Helix: Simple or Complex

Nucleic Acids Res. 2012 Jul;40(Web Server issue):W370-5. doi: 10.1093/nar/gks379. Epub 2012 May 7.


Transmembrane helical segments (TMs) can be classified into two groups of so-called 'simple' and 'complex' TMs. Whereas the first group represents mere hydrophobic anchors with an overrepresentation of aliphatic hydrophobic residues that are likely attributed to convergent evolution in many cases, the complex ones embody ancestral information and tend to have structural and functional roles beyond just membrane immersion. Hence, the sequence homology concept is not applicable on simple TMs. In practice, these simple TMs can attract statistically significant but evolutionarily unrelated hits during similarity searches (whether through BLAST- or HMM-based approaches). This is especially problematic for membrane proteins that contain both globular segments and TMs. As such, we have developed the transmembrane helix: simple or complex (TMSOC) webserver for the identification of simple and complex TMs. By masking simple TM segments in seed sequences prior to sequence similarity searches, the false-discovery rate decreases without sacrificing sensitivity. Therefore, TMSOC is a novel and necessary sequence analytic tool for both the experimentalists and the computational biology community working on membrane proteins. It is freely accessible at or available for download.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Hydrophobic and Hydrophilic Interactions
  • Internet
  • Membrane Proteins / chemistry*
  • Protein Structure, Secondary
  • Receptor, Cholecystokinin A / chemistry
  • Rhodopsin / chemistry
  • Sequence Analysis, Protein
  • Software*
  • User-Computer Interface


  • Membrane Proteins
  • Receptor, Cholecystokinin A
  • Rhodopsin