Given a query protein sequence, RAPTOR scans a template libary which is a set of known structures derived from the PDB. For each structure template, RAPTOR threads (aligns) the query sequence against the template by optimizing a scoring function and an optimal alignment will be obtained. After threading, all the alignments are ranked by a statistical measure. The structure of the query sequence is built on the alignment from the top template.

The scoring function used in RAPTOR includes terms associated with:

• Sequence homology
• Secondary structure types
• Solvent accessibility
• Pairwise interaction

The weights of different terms in the scoring function are optimized by using a generic algorithm.

RAPTOR provides three different threading algorithms:

• No Core: Dynamic programming used to align a query sequence to a template (algorithm used in PROSPECT)
• Non-Pairwise Core: Dynamic programming used to align the query sequence to the template (template parsed as a series of cores connected by loops)
• Integer Programming (Patented by BSI): Integer programming used to align the query sequence to the template. Pairwise interactions are treated rigorously (most servers cannot do this)
• Pairwise interaction

Statistical measures used to rank alignments:

• An SVM (Support Vector Machine) technique is used to rank the alignments after threading. The resulting score reflects the quality of the sequence-structure alignment.
• RAPTOR employs a BLAST-like E-value to evaluate a sequence-template alignment, which provides an overall measurement of prediction quality.

RAPTOR Workflow

RAPTOR takes the amino acid sequence and passes it to PSI-BLAST and SS Predictor for initial processing.

PSI-BLAST is a homology search tool that produces a profile that identifies key positions of conserved amino acids within a given motif. The SS Predictor is a secondary structure prediction tool that profiles the sequence in terms of likely secondary structure regions.

The next step in the workflow is the threading stage where the query sequence is aligned to templates in RAPTOR's template database.

To rank the templates in terms of alignment and structural similarity to the query sequence, the results of each stage is entered into a formula. The resulting score gives rise to a ranking and eValue.

The template database is a collection of archetypal protein structures that are each representative of a protein family or group.

The functional annotation is taken from the Protein Database (PDB) and a 3D structure can be obtained using the positional information in the PDB.