Schematic representation of the alignment procedure. First a HMM model is calculated for each TM domain from a manually curated alignment of the 7TM domains of 286 human GPCRs. Each HMM model is subsequently aligned to each GPCR sequence after which the ordering of the aligned helices is checked. In case of an incorrect ordering realignment is performed on smaller parts of the sequence. Finally the significance of each aligned helix is checked.