3D Macromolecular Structures
 
 
 
 
How to find structures with similarly shaped proteins or 3D domains, regardless of their degree of sequence similarity
 
 

As part of the data processing procedures at NCBI, all protein 3D structures in the Molecular Modeling Database (MMDB) have been compared against each other using the Vector Alignment Search Tool (VAST) in order to identify other structures that have similarly shaped proteins or 3D domains (substructures), based on purely geometrical criteria. These may represent distant homologs that cannot be recognized by sequence comparison alone. There are two ways to find structures that have similarly shaped proteins or 3D domains:


If your structure of interest is already available in the Entrez Structure (MMDB) database:

  • You can either:


    • Open the Entrez Structure (MMDB) database and retrieve a structure of interest (search tips). Once you are viewing the structure's summary page (for example, 1PTH), you can, scroll down to the table of "Molecules and interactions." Open the "show annotation" graphic (illustrated example) for any protein molecule of interest, then click on the bar graphic for the overall protein molecule or for any 3D domain it contains. That action will display a list of other structures that are similar in shape to the protein molecule or 3D domain you selected. (The VAST+ help document summarizes the difference between VAST and VAST+ and provides illustrated examples of each type of output.)

      OR


    • Open the VAST home page and enter the PDB ID or MMDB ID of your query structure into the "Show Similar Structures for:" text box that appears in the middle of the page. By default, the system will display the new style VAST+ results, which lists structures based on their similarity to the macromolecular complex of your query structure. From that page, you can follow the "Original VAST" link to display a table (illustrated example) that lists each protein molecule and 3D domain in the query structure, along with the number of structures that contain a similarly shaped protein molecule or 3D domain. Click on any link in that table to view the structures that are similar in shape to the individual protein molecule or 3D domain of interest.


  • Regardless of which of the above approaches you use:


    • The VAST results page will show a subset of similar structures by default, because the number of hits can be large. You can use the "List" option to control the number of VAST hits you see by selecting a desired redundancy level, or to view All Sequences, if desired.


    • Use the check boxes to select hits of interest and press the "View 3D Alignment" button to view your structure superposed onto the geometrically similar structure in Cn3D, along with a corresponding sequence alignment (illustrated example). Please note that, in order for the "View 3D Alignment" button to work, the Cn3D program must be present on your computer. It is a free helper application available for Windows, Macintosh, and Unix platforms. Installation takes only a couple of minutes and a tutorial describes the program's features and functions.


If you would like to find structures that have a similarly shaped biological assembly to your query structure, rather than structures that have similarly shaped individual proteins or 3D domains, then follow the steps in "How to find structures with similarly shaped biological assemblies, regardless of their degree of sequence similarity. [VAST+]."



If your structure of interest is not yet available in the Entrez Structure (MMDB) database, then follow the steps in "How to compare a newly resolved 3D structure in PDB format against the 3D coordinates of structures in MMDB."

 
 
 
Revised 12 February 2016