Biology Reference
In-Depth Information
Fig. 4 Schematic overview of the TM-aware strategy in PRALINE. For details, see text. Adapted from ref.
37
PHOBIUS [
38
], TMHMM [
39
], or HMMTOP [
40
]. Secondly,
TM-specific substitution scores from the PHAT [
41
] matrix are
used to align residues that are predicted to be members of a TM
segment (Fig.
4
). The remaining soluble fragments are aligned
using the generic BLOSUM62 matrix.
A tree-based consistency iteration scheme is then performed to
enhance the MSA quality, which is similar to the tree-dependent
partitioning method proposed by Hirosawa et al. [
42
] and its
implementation in the MUSCLE alignment tool [
43
,
44
]. In this
scheme each edge of the guide tree is used to divide the alignments
into two sub-alignments, which are then successively realigned.
A new alignment is selected only if the alignment score is higher
than the current score. The alignment score in the TM-aware
alignment strategy is calculated as the sum of the substitution values
of the BLOSUM and PHAT matrices (depending on the TM
topology of the alignment positions). One iterative cycle in this
tree-based consistency strategy is completed when each edge of the
guide tree is visited once. The maximum number of iteration cycles
has been set to 20 [
37
].
The PRALINE server is accessible via the Web site of the IBIVU
center at VU University Amsterdam (URL:
http://www.ibi.vu.nl/
programs/PRALINEwww/
)
. The server is aimed to assist both
specialist and nonspecialist users. It provides the user with extensive
online documentation for each of the different parameters PRA-
LINE may be run with, and also provides a “sample output” page
which contains examples of the possible outputs of the PRALINE
server using the various alignment strategies described above. PRA-
LINE accepts sequences in FASTA [
45
] format as input. For each
alignment job, the maximum number of sequences that can be
2.6 The PRALINE
Online Server
