Protein downloading structures from

Figure 5.5 Retrieval of protein structure from Protein Data Bank The atomic coordinates of protein three-dimension structures can be retrieved from PDB (http //www.rcsb.org/pdb) by entering PDB id (e.g. IRNO) or keyword (e.g. pancreatic ribonuclease). The query search returns a list of hits from which the desired PDB file can be selected (click Explore), then viewed (select View structure as shown), analyzed (select Structure neighbor. Geometry or Sequence detail) and retrieved (select Download/Display file).

Biophys. Biomolec. Struct., 29, 291 (2000). Comparative Protein Structure Modeling of Genes and Genomes. Download MODELLER from http //salilab.org/modeler/. 

PROCHECK A Program to Check the Stereochemical Quality of Protein Structures. Download PROCHECK from http //www.biochem.ucl.ac.uk/ roman/ procheck/procheck.html. 

The structure of human muscle fructose-1,6-bisphosphate aldolase, as determined by X-ray crystallography and downloaded from the Protein Data Bank. (PDB ID 1ALD Gamblin, S. J., Davies, G. J., Grimes, J. M., Jackson, R. M., Littlechild, J. A., Watson, H. C. Activity and specificity of human aldolases. J. Mol. Biol. v219, pp. 573-576, 1991.)... 

Another useful structure tool is RasMol (or RasMac). This will allow you to view the detailed structure of a protein and rotate it on coordinates so you can see it from all perspectives. A hyperlink to RasMol is present under the View Structure function just above Chime. You may need to study RasMol instructions provided under Help, or you may use a Ra.s Mol tutorial listed in Table El.2. Another useful protein viewer is tin-Swiss-Protein Pdv Viewer (Table El.2). BLAST is an advanced sequence similarity tool available at NCBI. To access this, go to the NCBI home page (www.ncbi.nlm.nih.gov) and click on BLAST. Then click on Basic BLAST search to obtain a dialogue box into which you may type the amino acid sequence of human a-lactalbumin. This process may be stream lined by downloading the amino acid sequence in FASTA format into a file and transferring the fde into the BLAST dialogue box. BLAST will provide a list of proteins with sequences similar to the one entered. 

Another way to get a structure into the computer is to import (read) a molecule file containing the atomic co-ordinates (and perhaps other atomic and molecular information) into your program. Unfortunately, there is no single standard file format that all programs use. However, some of the commonly encountered formats include those of SYBYL MOL2 files and Protein Data Bank (PDB) files. There are also free programs available for download from the World Wide Web that can interconvert the numerous file formats still in use. 

The Protein Data Bank (PDB, http //www.rcsb.org/pdb/) is the de facto repository for macromolecular structures resolved by NMR or diffraction methods [42]. The structures of many protein-ligand complexes have been resolved and their atomic coordinates can be downloaded from the PDB web portal for further analysis. 

The final method of RNA structure prediction, empirical algorithms, are also analogous to primary-structure motif detection methods. Known RNA structural motifs are extracted from structural databases, and the primary-structure patterns underlying these motifs are identified. Novel RNA sequences are then scanned for these primary-structure motifs much like a novel protein sequence might be scanned for CDs. In essence, these methods search the primary structure of sequences for conserved motifs that indicate secondary structure. One of the most flexible and powerful empirical tools is RNAMotif, which is freely available for download, but does not have an associated web-server (23). 

The common atomic coordinate files for 3D structure in biochemistry is PDB format. The pdb files of polysaccharides, proteins, and nucleic acids can be retrieved from the Protein Data Bank at RCSB (http //www.rcsb.org/pdb/). On the home page (Figure 4.15), enter PDB ID (check the box query by PDB id only ) or keywords (check the box match exact word ) and click Find a structure button. Alternatively, initiate search/retrieval by selecting SearchLite. On the query page, enter the keyword (e.g., the name of ligand or biomacromolecule) and click Search button. Select the desired entry from the list of hits to access Summary information of the selected molecule. From the Summary information, select Download/Display file and then PDB Text and PDB noncompression format to retrieve the pdb file. In order to display 3D structure online, choose View structure followed by selecting one of 3D display options. The display can be saved in. jpg or. gif image format. 

Download the AutoDock 4.2 package from http //www.aut-odock.scripps.edu/ to dock the modeling protein structure and small molecules for virtual screening for potential antibiotics binding the active site. The structure of one such potential antibiotic (enoxacin) is shown in Fig. 4. If we assume that a given pocket is important for the function of the protein, we screen for small molecules that can dock to that site. 

Computational results were obtained using Spartan 08 (Wavefunction Inc., Irvine, CA) and software programs from Accelrys Software Inc. with graphical displays generated by the Discovery Studio Visualizer. Where protein structures have been downloaded from the RCSB Protein Data Bank the full references and PDB IDs have been given. I wish to acknowledge the use of the Chemical Database Service at Daresbury for access to other crystal structures. Again, full primary sources can be found in the references. 

Crystal structures are stored in formatted text files called "PDB" files. These files can be freely downloaded from the RCSB Protein Data Bank at http //www.pdb.org. Information on how to search and navigate the PDB is available on the PDB home page. 

Scientists have developed powerful techniques for the determination of protein structures, as will be considered in Chapter 3. In most cases, these techniques allow the positions of the thousands of atoms within a protein structure to be determined. The final results from such an experiment include the x, y, and z coordinates for each atom in the structure. These coordinate files are compiled in the Protein Data Rank (http //www. rcsb.org/pdb/) from which they can be readily downloaded. These structures comprise thousands or even tens of thousands of atoms. The complexity of proteins with thousands of atoms presents a challenge for the depiction of their structure. Several different types of representations are used to portray proteins, each with its own strengths and weaknesses. The types that you will see most often in this book are space filling models, bail-and-stick models, backbone models, and ribbon diagrams. Where appropriate, we note structural features of particular importance or relevance in an illustration s legend. 

Illustrations with organic structural formulae have been used widely. In depicting sugar rings. Mills formulae have been used if the conformation is not known with confidence, otherwise conformational structures are drawn. Ribbon diagrams of various carbohydrate-active proteins with known structures are available from protein databases. Their reproduction in this book would have increased its cost and, at a time when all beginning researchers have Web access, only marginally increased its usefulness. If the reader wants to know what, say, a GH6 cellulase looks like, he or she should go to CAZy, the wonderful resource for the whole scientific community started by Bernard Henrissat and maintained by him and Pedro Coutinho, and click on the links in the 3D column. The protein can then be viewed in various downloadable viewers. 

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