Category Proteomics>Protein Structure/Modeling Systems/Tools

Abstract RAPTOR (RApid Protein Threading PredictOR) is an innovative software tool designed for accurate protein structure prediction. It combines advanced analysis tools in one integrated software solution and provides three (3) different threading methods.

RAPTOR’s unique integer programming optimization approach is most effective for finding structure templates of targets with low sequence homology and is able to generate high quality models.

The easy-to-use interface and easy-to-understand E-values are ideal for beginners and experts. Above all, the intuitive display of the output enables users to understand the results simply at a glance.

RAPTOR’s Approach to Prediction --

Given a query protein sequence, RAPTOR scans a template library which is a set of known structures derived from the Protein Data Bank (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; and Pairwise interaction.

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

RAPTOR provides three (3) different threading algorithms -

No Core; Non-Pairwise (NP) Core; Integer Programming (IP) - (Patented by BSI) and Pairwise interaction. (See ‘Threading engines’ below…).

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 Basic Local Alignment Search Tool (BLAST)-like E-value to evaluate a sequence-template alignment, which provides an overall measurement of prediction quality.

RAPTOR Components --

Threading engines -- No Core, NP Core and IP are the three (3) different threading engines implemented in RAPTOR (as stated above…). No Core and NP Core are based on dynamic programming and faster than IP.

The difference between them is that in NP Core, a template is parsed into many “core” regions. A core is a structurally conserved region. IP is RAPTOR’s unique integer programming-based threading engine.

It produces better alignments and models than the other two (2) threading engines. Users can always start with No Core and NP Core. If their predictions are Not good enough, IP may be a better choice. After all three (3) methods are run; a simple consensus may help to find the best prediction.

3D structure modeling module - The default 3D structure modeling tool used in RAPTOR is OWL (see below...).

Three-dimensional structure modeling involves two steps. The first step is ‘loop modeling’ which models regions in the target sequence that map to nothing in the template. After all the loops are modeled and the backbone is ready, side chains are attached to the backbone and packed up.

For loop modeling, a cyclic coordinate descent algorithm is used to fill the loops and avoid clashes. For side chain packing, a tree decomposition algorithm is used to pack up all the side chains and avoid any clashes. OWL is automatically called in RAPTOR to generate the 3D output.

If a researcher has MODELLER (additional software tool…); they can also set up RAPTOR to call MODELLER automatically.

RAPTOR can also generate ICM-Pro input files, which users can use to run ICM-Pro with (ICM-Pro is a desktop-modeling environment).

OWL Modeling - OWL is a modeling software package for homology or comparative modeling of protein 3D structures.

It uses a comparative modeling methodology to automatically generate a refined 3D homology model of a protein sequence containing all non-hydrogen atoms, given a sequence alignment to a known 3D protein structure.

Loops in the sequence are connected by OWL using state-of-the-art fragment assembly technology, also available in FALCON (an additional software product/method), based on an all-atom energy function and a new conditional random field sampling technique. Side chains are modeled by a new tree-decomposition approach, fast and accurately.

PSI-BLAST module - To make it a comprehensive tool set, Position Specific Iterative-Basic Local Alignment Search Tool (PSI-BLAST) is also included in RAPTOR to let users do homology modeling. Users can set up all the necessary parameters by themselves.

There are two (2) steps involved in running PSI-BLAST. The first step is to generate the sequence profile.

For this step, the (NR) non-redundant database is used. The next step is to let PSI-BLAST search the target sequence against the sequences from the Protein Data Bank (PDB). Users can also specify their own database for each step.

Protein structure viewer - There are many different structure viewers. In RAPTOR, Jmol - (Jmol is an open-source Java viewer for chemical structures in 3D) is used as the structure viewer for examining the generated prediction.

Raptor Output - After a threading/PSI-BLAST job, one can see a ranking list of all the templates. For each template, users can view the alignment, Expectation value (E-value), and numerous other specific scores.

Also, the functional information of the template and its SCOP classification are provided [The Structural Classification of Proteins (SCOP) database is a largely manual classification of protein structural domains based on similarities of their amino acid sequences and three-dimensional structures]. One can also view the sequence’s PSM matrix and secondary structure prediction.

If a template has been reported by more than one method, it will be marked with the number of times it has been reported. This helps to identify the best template.

RAPTOR Features/capabilities --

1) Unique Threading Algorithm - RAPTOR offers three (3) threading algorithms: two based on dynamical programming (DP) and one based on integer programming (IP). The DP algorithms effectively handle most easy sequences (high homology). For hard sequences (low homology), the IP algorithm gives a confident prediction.

2) Supreme Accuracy - RAPTOR has superior recognition of structure similarities at the fold, family and super family levels. It delivers high accuracy alignments and models, as demonstrated in recent community-wide tests.

3) Conservation Discovery - RAPTOR has proven its ability to find structural conservation that is otherwise unnoticed by most threading algorithms.

RAPTOR’s unique integer programming algorithm takes pairwise contact potential into consideration when doing threading, which has greatly enhanced the prediction accuracy.

4) Up-To-Date Template Library - The structure template library used in RAPTOR is a representative subset of the PDB database. As the PDB is constantly updated, BSI provides template updates every three (3) months.

5) Easy to Install and Use - Installation of RAPTOR is fully automated and users just need to specify the installation path.

A friendly graphical user interface (GUI) enables even beginners to start quickly. With the preset configuration, users simply need to click the Run button to obtain final results.

6) Intuitive Output - The intuitive output makes it possible to understand relevant data at a glance. E-values enable users to easily judge the significance of the prediction. The color matrix representing sequence profiles help users to easily identify the conservative residues.

The colors representing different types of secondary structures in the PIR format alignment allow users to compare the target and template comprehensively.

RasMol is used to help users to examine the predicted structures in 3D space.

7) Flexible Interface - RAPTOR works seamlessly and can be configured to call Modeller automatically.

8) Parallel Computing - The threading process is parallelized in RAPTOR.

RAPTOR can run in a distributed environment, clusters or on Symmetric Multi-Processing (SMP) machines, which will substantially reduce run time.

System Requirements

RAPTOR supports both Windows and Linux. The latest versions of RAPTOR have been fully tested on Windows XP, 2000 and Vista. For Linux, current versions of RAPTOR have been tested on Fedora and Ubantu.


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G6G Abstract Number 20713

G6G Manufacturer Number 100432