PROTEIN TERTIARY STRUCTURE Sites are offered for calculating and displaying the 3-D structure of oligosaccharides and proteins. With the two protein  analysis sites the query protein is compared with existing protein structures as revealed through homology analysis.

Background: "Principles of Protein Structure, Comparative Protein Modelling and Visualization" by N. Guex & M.C.  Peitsch (GlaxoWellcome, Switzerland) is here. To obtain PDB coordinates for a protein of your interest, go to the Protein Data Bank or Molecules to Go  or NCBI.

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red_bullet.gif (914 bytes)  PHYRE2 - Protein Homology/analogY Recognition Engine - this is my favourite site for the prediction of the 3D structure of proteins.  In each case I have used this site it has provide me with a model. Phyre2 uses the alignment of hidden Markov models via HHsearch to significantly improve accuracy of alignment and detection rate.  It also incorporates a new ab initio folding simulation called Poing to model regions of your proteins with no detectable homology.

red_bullet.gif (914 bytes) CPHModels (Center for Biological Sequence Analysis, Technical University of Denmark) - currently consists of the following tools: Sowhat: A neural network based method to predict contacts between C-alpha atoms from the amino acid sequence. RedHom: A tool to find a subset with low sequence similarity in a database. Databases: Subsets of the Brookhaven Protein Data Bank (PDB) database with low sequence similarity produced using the RedHom tool.

red_bullet.gif (914 bytes) SWISS-MODEL - (Glaxo-Wellcome Experimental Research, Switzerland)  An automated comparative protein modelling server. Choose "First Approach mode". N.B. results come by E-mail and require a viewer such as DeepView - Swiss-PdbViewer, Rasmol, Cn3D v3.0 or WebMol Java PDB Viewer to visualize. 

red_bullet.gif (914 bytes) I-TASSER ONLINE - 3D models are built based on multiple-threading alignments by LOMETS and iterative TASSER simulations; function inslights are then derived by matching the predicted models with protein function databases. I-TASSER was ranked as the No 1 server for protein structure prediction in recent CASP7 and CASP8 experiments. (Reference: A. Roy et al. 2010. Nature Protocols 5: 725-738)

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LOOPP (Learning, Observing and Outputting Protein Patterns) (Computational Biology Service Unit, Cornell Univ., U.S.A.) is a fold recognition program based on the collection of numerous signals, merging them into a single score, and generating atomic coordinates based on an alignment into a homologue template structure. The signals we are using include straightforward sequence alignment, sequence profile, threading, secondary structure and exposed surface area prediction. Excellent.

red_bullet.gif (914 bytes) ESyPred3D - this automated homology modeling program derives benefit from a new alignment strategy using neural networks. Alignments are obtained by combining, weighting and screening the results of several multiple alignment programs. The final three dimensional structure is built using the modeling package MODELLER. (Reference: C. Lambert et al. 2002. Bioinformatics 18: 1250-1256).

red_bullet.gif (914 bytes) AS2TS system - offers a variety of resources for protein structural analysis using the LGA (local-global alignment) program to search for regions of local similarity and to evaluate the level of structural similarity between compared protein structures. To facilitate the homology-based protein structure modeling process, the AL2TS service translates given sequence–structure alignment data into the standard PDB coordinates (Reference: A. Zemla et al. 2005. Nucl. Acids Res. 33: W111-W115).

red_bullet.gif (914 bytes) 3D-JIGSAW (Biomolecular Modelling Laboratory, Cancer Research UK, England) - homology modelling. Save email results as *.pdb and view with Rasmol etc.

red_bullet.gif (914 bytes) RaptorX - consists of four major modules: single-template threading, alignment quality assessment, and multiple-template threading. (Reference: Källberg, M. et al. 2012. Nat Protoc. 7(8):1511-1522).

  red_bullet.gif (914 bytes)  WHAT IF Web Interface (Centre for Molecular and Biomolecular Informatics, University of Nijmegen, Holland) offers one a large number of tools for examining PDB files.

red_bullet.gif (914 bytes) Protein Peeling: an approach for splitting a 3D protein structure into compact fragments -  a method to identify small compact units (protein units (PU)) that compose protein three-dimensional structures. (Reference:  J.-C. Gelly et al. 2006. Bioinformatics 22: 129-133)

red_bullet.gif (914 bytes) InterProSurf (Reference: S.S. Negi et al. 2007. Bioinformatics. 23: 3397-3399) - predicts interacting amino acid residues in proteins that are most likely to interact with other proteins, given the 3D structures of subunits of a protein complex. The prediction method is based on solvent accessible surface area of residues in the isolated subunits, a propensity scale for interface residues and a clustering algorithm to identify surface regions with residues of high interface propensities.

red_bullet.gif (914 bytes) ProtSkin converts a protein sequence alignment in BLAST, CLUSTAL or MSF format to a property file used to map the sequence conservation onto the structure of a protein using the GRASP, MOLMOL or PyMOL. A pseudo-PDB file with the sequence conservation score in place of the temperature factor is also provided, to use with programs such as InsightII (accelrys). (Reference: Deprez, C. et al. 2005. J. Mol. Biol. 346: 1047-1057)

Structures derived from NMR coordinates

red_bullet.gif (914 bytes) GeNMR (GEnerate NMR structure) - generates 3D protein structures using NOE-derived distance restraints and NMR chemical shifts. (Reference: M. Berjanskii et al. 2009. Nucl. Acids Res. 37(Web Server issue):W670-W677)

Once you have a structure you may want to superimpose it on other molecules. To obtain PDB accession codes for a protein of your interest, go to the Protein Data Bank

red_bullet.gif (914 bytes) FATCAT (Flexible structure AlignmenT by Chaining Aligned fragment pairs allowing Twists) is an approach for flexible protein structure comparison. It simultaneously addresses the two major goals of flexible structure alignment; optimizing the alignment and minimizing the number of rigid-body movements (twists) around pivot points (hinges) introduced in the reference structure. (Reference: Y.Ye & A. Godzik. (2003) Bioinformatics 19: suppl. 2. ii246-ii255).

red_bullet.gif (914 bytes) Dali Server - this is a network service for comparing protein structures in 3D. You submit the coordinates of a query protein structure and Dali compares them against those in the Protein Data Bank (PDB). You receive an email notification when the search has finished. In favourable cases, comparing 3D structures may reveal biologically interesting similarities that are not detectable by comparing sequences. Once you have a match you can use the pairwise DaliLite server to compare them.

red_bullet.gif (914 bytes) Search for Similar Protein Structures by FATCAT  - either upload local PDB files or simply provide PDB codes. For close homologs go here (Reference: Y. Ye & A. Godzik. 2003. Bioinformatics 19(Suppl 2):II246-II255)

red_bullet.gif (914 bytes) SuperPose - is a protein superposition server. It calculates protein superpositions using a modified quaternion approach. From a superposition of two or more structures, SuperPose generates sequence alignments, structure alignments, PDB coordinates, RMSD statistics, Difference Distance Plots, and interactive images of the superimposed structures.  The SuperPose web server supports the submission of either PDB-formatted files or PDB accession numbers. (Reference: Maiti, R. et al. 2004. Nucleic Acids Res. 32 (Web Server issue: W590-594).

red_bullet.gif (914 bytes) iPBA - is a tool for comparison of protein structures based on similarity in the local backbone conformation. It presents an improved alignment approach using (i) specialized PB Substitution Matrices (SM)
and (ii) anchor-based alignment methodology. (Reference: Gelly, J.C. et al. 2011. Nucleic Acids Res. 39(Web Server issue):W18-23).

red_bullet.gif (914 bytes) MAPSCI Multiple Alignment of Protein Structures and Consensus Identification. The algorithm represents each
protein as a sequence of triples of coordinates of the alpha-carbon atoms along the backbone. It then computes iteratively a sequence of transformation matrices (i.e., translations and rotations) to align the proteins in space and generate the consensus. The algorithm is a heuristic in that it computes an approximation to the optimal alignment that minimizes the sum of the pairwise distances between the consensus and the transformed protein. (Reference: Ilinkin, I. et al. 2010. BMC Bioinformatics. 11:71).

Presentation of data:

red_bullet.gif (914 bytes) CEP: a conformational epitope prediction server - provides a web interface to conformational epitope prediction. The algorithm, apart from predicting conformational epitopes, also predicts antigenic determinants and sequential epitopes. The epitopes are predicted using 3D structure data of protein antigens, which can be visualized graphically. (Reference: U. Kulkarni-Kale et al. 2005.  Nucl. Acids Res. 33: W168-W171). The following is an example of an epitope (space-filled) mapped onto the partial surface (stick) of lysozyme:

red_bullet.gif (914 bytes) PDB2MultiGIF (Central Spectroscopy Department - Molecular Modeling, Deutsches Krebsforschungszentrum, Germany) - if you want to present your model on a webpage in a similar manner to the three pictures on the entry page use this program. It takes the 3D structure (PDB file) and generates an animated image which can be displayed using any browser. There is considerable choice on the image size, number of frames and direction of rotation.

red_bullet.gif (914 bytes) Protein Picture Generator - generates static or animated pictures from a protein structure file (PDB). Offers a huge number of controls on the presentation format. (Reference: C. Binisti et al. 2005. Nucl. Acids Res. 33: W320- W323).

red_bullet.gif (914 bytes) MovieMakera web server that allows short (~10 sec), downloadable movies to be generated of protein dynamics. It accepts PDB files or PDB accession numbers as input and automatically outputs colorful animations covering a wide range of protein motions and other dynamic processes. Users have the option of animating 1) simple rotation 2) morphing between two end conformers 3) short-scale, picosecond vibrations; 4) ligand docking; 5) protein oligomerization; 6) mid-scale nanosecond (ensemble) motions; and 7) protein folding/unfolding.  MovieMaker is not a molecular dynamics server and does not perform MD calculations. (Reference: R. Maiti et al. 2005. Nucl. Acids Res. 33: W358-W362)

red_bullet.gif (914 bytes) COMBOSA3D - Coloring Of Molecules Based On Sequence Alignment (Paul Stoddard) - accepts a group of pre-aligned sequences in FASTA format (one of the sequences must have a solved three-dimensional structure), and it uses the alignment information to highlight conserved residues on the molecule. Three-dimensional structures are shown using a Chime plugin or one may use RasMol to view and color a molecule..

Data mining:

red_bullet.gif (914 bytes) ProFunc: a server for predicting protein function from 3D structure - this program takes PDB files and carries out an awesome array of analyses including scans against PDB and motif databases, determination of surface morphology and conserved residues, and potential ligand-binding sites. (Reference: R. A. Laskowski et al. 2005. Nucl. Acids Res. 33: W89-W93).
red_bullet.gif (914 bytes) Pocket-Finder (Bioinformatics,
University of Leeds, Great Britain) - is a pocket detection algorithm which works by scanning a probe radius 1.6 angstoms along all gridlines of a grid resolution 0.9 angstroms surrounding the protein. The probe also scans cubic diagonals. Grid points are defined to be part of a site when the probe is within range of protein atoms followed by free space followed by protein atoms. Since the protein is scanned in seven directions, each grid point can be defined to be part of a site up to seven times. Grid points are only retained if they are defined to be part of a site at least five times.

red_bullet.gif (914 bytes) Q-SiteFinder (Bioinformatics, University of Leeds, Great Britain) - is a new method of ligand binding site prediction. It works by binding hydrophobic (CH3) probes to the protein, and finding clusters of probes with the most favorable binding energy. These clusters are placed in rank order of the likelihood of being a binding site according to the sum total binding energies for each cluster.

red_bullet.gif (914 bytes) P-cats - Prediction of CATalytic residueS in proteins - predicts the catalytic residues in proteins from the atomic coordinates. (Reference: K. Kinoshita & M. Ota. 2005. Bioinformatics 2005 21: 3570-3571)

Predict Function from Structure:

red_bullet.gif (914 bytes) ProFunc - is been developed to help identify the likely biochemical function of a protein from its three-dimensional structure using a variety of sequence- and structure-based methods (Reference: Laskowski R.A. et al. 2005. Nucleic Acids Res.33, W89-W93).

Metasite:

red_bullet.gif (914 bytes) Scratch Protein Predictor - (Institute for Genomics and Bioinformatics, University California, Irvine) - programs include: ACCpro: the relative solvent accessibility of protein residues; CMAPpro: Prediction of amino acid contact maps; COBEpro: Prediction of continuous B-cell epitopes; CONpro: predicts whether the number of contacts of each residue in a protein is above or below the average for that residue; DIpro: Prediction of disulphide bridges; DISpro: Prediction of disordered regions; DOMpro: Prediction of domains; SSpro: Prediction of protein secondary structure; SVMcon: Prediction of amino acid contact maps using Support Vector Machines; and, 3Dpro: Prediction of protein tertiary structure (Ab Initio).

 

Updated: October 28, 2012