Reprojections of the averaged model were used to refine alignment of all selected segment images.
Refined alignment and sequence to structure mapping was performed in Insight II and with Slide, a interactive threading software [38].
The manually refined alignment is shown in the Supporting Information.
These were then combined using the profile alignment feature of MUSCLE, and the global alignment was subsequently updated using the "refine alignment" option.
Delete the columns with more than 75% gaps from Ao to obtain a refined alignment A. Compute the pseudo-energy e ij for every pairing column (i, j) in A as in Equation (16).
Delete the columns with more than 75% gaps from A o to obtain a refined alignment A. Compute the pseudo-energy e ij for every pairing column (i, j ) in A as in Equation (16).
All raw LC-MS/MS data were imported and subjected to chromatographic retention time alignment using the PeakTeller® algorithm with a minimum peak time width set to 6 s, alignment search distance set to 4 min and the refine alignment option enabled.
Sequence sets (protein or nucleotide) were aligned with Muscle [ 41], and manually refined (alignments are available upon request).
HMMs for each subfamily were used to determine subfamily membership and refine alignments.
Because of its high speed and low number of artefacts evident upon visual inspection, we chose Mafft version 5, which refines alignments iteratively using pairwise alignment information.
