3D Structures of Proteins and Nucleic Acids--Lab
There are several areas you can explore in this session.
In the RCSB Protein Data Bank (PDB), you can locate the xyz coordinates of protein structures and download them for use on your computer with other software, and there are several tools there for viewing the structure directly. The database contains proteins (and a few nucleic acids and carbohydrates) whose structures have been determined crystallographically, or by NMR, or by computer modeling.
You may wish to see if a protein of interest to you has been placed in the database. On the Protein Data Bank page, select SearcLite (simple keyword search) or SearchFields (advanced searching tools). If you wish to find tryptophan synthase, for example, just type "tryptophan synthase" in the Keyword field and hit the "Search" button. You will get a "Query Results" page. In the case of tryptophan synthase, there are currently 20 structures released and 2 more being processed. To retrieve one of these, select an entry and hit the "Retrieve Data" button. This will give you a page with links to the PDB file (header information only, or the complete listing with xyz coordinates), sequence files, coordinates in other file formats, perhaps some graphics files in GIF, JPEG, or SGI format, and a variety of other information, depending on what is available for your particular protein.
Look at the header information! It often tells you a lot about the structure you are interested in--journal references, information about cofactors or other ligands in the crystal, parts of the structure which were not solved, secondary structure features, sequence, and more. If you choose the "complete with coordinates" button, you will get the full PDB file, containing xyz coordinates for each atom of the molecule. Many programs (e.g., RasMol, KineMAGE) are able to read these files and display the structures.
PDB also has some tools for viewing the structures in your web browser.
The Nucleic Acid Database (NDB) is a structural database similar in some respects to PDB, except that the focus is on nucleic acid structures. There are A-, B-, and Z-DNA structures, DNA complexed with various drugs, single- and double-stranded RNA, transfer RNA, ribozymes, some DNA-RNA hybrids, and some nucleic acid-protein complexes.
The NIH runs a site called Molecules To Go which provides several options for viewing Brookhaven PDB structures with your web browser or with programs such as RasMol. Start by entering one or more keywords in the search field. If you enter "ribonuclease" for example, you will get a list of 200 structures. Select one of these and you will get a request form which lets you customize the view you get. Press on the button labelled "PDB Viewer" and select one of the "Image" formats, such as "Ball and Stick Image," then "Submit Request." Your picture will appear in the browser window. If you go back to the request form, you can choose to rotate the image around the x, y, and z axes, choose a different coloring scheme, and look at different kinds of images. When you do this, the image may not change! Web browsers try to be efficient--if you request a file that it thinks you already downloaded recently, it may just bring back the local copy it has stashed away. In this case, pick the "Reload" button on your browser, and a fresh copy will be downloaded. Molecules R US also gives you the first 100 lines of header information from the PDB file.
Two or more proteins can be aligned in three dimensions at a site called CE - Combinatorial Extension of the Optimal Path (A Method for Finding 3-D Similarities in Protein Structures), by Ilya Shindyalov and Phil Bourne. The first menu choice is to "Align Two Chains." Their default example compares the A and B chains of deoxyhemoglobin. You can enter PDB identifiers to compare other structures. For example, you can enter "1PFK" and "3PFK" to compare phosphofructokinases of E. coli and Bacillus stearothermophilus. CE's "Compare All" feature lets you input a structure and search for other proteins with similar protein folds. For example, if you specify E. coli phosphofructokinase (1PFK), the search will return all the other PFK structures as well as other proteins which have a similar 3D structure. Compare 1PFK with 1PHP, 3-phosphoglycerate kinase. 1PHP is about twice the size of 1PFK, but there is a very large domain which has a fold which is very similar to 1PFK.