title: Prediction of transmembrane helix orientation in polytopic membrane proteins.
abstract: BACKGROUND
  Membrane proteins compose up to 30% of coding sequences within genomes. However, their structure determination is lagging behind compared with soluble proteins due to the experimental difficulties. Therefore, it is important to develop reliable computational methods to predict structures of membrane proteins.
  
  
  RESULTS
  We present a method for prediction of the TM helix orientation, which is an essential step in ab initio modeling of membrane proteins. Our method is based on a canonical model of the heptad repeat originally developed for coiled coils. We identify the helical surface patches that interface with lipid molecules at an accuracy of about 88% from the sequence information alone, using an empirical scoring function LIPS (LIPid-facing Surface), which combines lipophilicity and conservation of residues in the helix. We test and discuss results of prediction of helix-lipid interfaces on 162 transmembrane helices from 18 polytopic membrane proteins and present predicted orientations of TM helices in TRPV1 channel. We also apply our method to two structures of homologous cytochrome b6f complexes and find discrepancy in the assignment of TM helices from subunits PetG, PetN and PetL. The results of LIPS calculations and analysis of packing and H-bonding interactions support the helix assignment found in the cytochrome b6f structure from green alga but not the assignment of TM helices in the cyanobacterium b6f structure.
  
  
  CONCLUSIONS
  LIPS calculations can be used for the prediction of helix orientation in ab initio modeling of polytopic membrane proteins. We also show with the example of two cytochrome b6f structures that our method can identify questionable helix assignments in membrane proteins. The LIPS server is available online at http://gila.bioengr.uic.edu/lab/larisa/lips.html.
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, M/C 563, 835 S, Wolcott St, Chicago, IL 60612-7340, USA. larisa@uic.edu
authors.forename: Larisa
authors.initials: L
authors.lastname: Adamian
authors.forename: Jie
authors.initials: J
authors.lastname: Liang
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D000460:Chlorophyta / Q000737:chemistry; D019295:Computational Biology / Q000379:methods*; D045346:Cytochrome b6f Complex / Q000737:chemistry; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry; D040681:Structural Homology, Protein; D050916:TRPV Cation Channels / Q000737:chemistry
chemical_list: D008563:Membrane Lipids; D008565:Membrane Proteins; D021122:Protein Subunits; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D045346:Cytochrome b6f Complex