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Fold Recognition and Accurate
Sequence-Structure Alignment of Sequences Directing β-Sheet Proteins
Andrew V. McDonnell, Matthew Menke, Nathan Palmer, Jonathan King, Lenore
Cowen & Bonnie Berger
Abstract
The ability to predict structure from sequence is particularly important
for toxins, virulence factors, allergens, cytokines, and other proteins
of public health importance. Many such functions are represented in the
parallel β-helix and β-trefoil families. A method using pairwise
β-strand interaction probabilities coupled with evolutionary information
represented by sequence profiles is developed to tackle these problems
for the β-helix and β-trefoil folds. The algorithm BetaWrapPro
employs a "wrapping" component which may capture folding processes with
an initiation stage followed by progressive interaction of the sequence
with the already-formed motifs. BetaWrapPro outperforms all previous motif
recognition programs for these folds, recognizing the β-helix with
100% sensitivity and 99.7% specificity and the β-trefoil with 100%
sensitivity and 92.5% specificity, in cross-validation on a database of
all non-redundant known positive and negative examples of these fold classes
in the PDB. It additionally aligns 88% of residues for the β-helices
and 86% for the β-trefoils accurately (within four residues of the
exact positon) to the structural template, which is then used with the
side-chain packing program SCWRL to produce 3D structure predictions.
One striking result has been the prediction of an unexpected parallel
β-helix structure for a pollen allergen, and its recent confirmation
through solution of its structure. A web
server running BetaWrapPro is available and outputs putative PDB-style
coordinates for sequences predicted to form the target folds
References:
[1] Andrew V. McDonnell, Matthew Menke, Nathan Palmer, Jonathan King,
Lenore Cowen & Bonnie Berger. Fold Recognition and Accurate Sequence-Structure
Alignment of Sequences Directing beta-Sheet Proteins. Proteins: Structure,
Function, and Bioinformatics, in press, 2006. |
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