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SMART Protein Modeling

SMART Project Protein Structure and Folding: The WSSP has teamed up with the Center for BioMolecular Modeling to provide students with the opportunity of creating a physical model of a homolog of one of the proteins that was identified in the screen of the cDNA library. The WSSP will pay for the costs for one model for each school.  Schools can do more than one model if they provide additional support ($250/model) to cover the costs of printing the structure. High Schools wishing to create a physical model of their protein need to provide the following information by e-mail to Susan Coletta:

1. A .doc file with the following information
  a. School name
  b. Names of students participating in the project
  c. Name of teacher who worked with the students
  d. Protein Data Bank (PDB) file name (e.g. 1A3N.pdb)
  e. Name of the protein modeled (e.g. Hemoglobin) NOTE: This cannot be the clone that was modeled at the summer Institute.
  f. Primary citation associated with the pdb file (e.g. Tame, J.R., Vallone, B. (2000) The structures of deoxy human haemoglobin and the mutant Hb Tyralpha42His at 120 K. Acta Crystallogr.,Sect.D 56: 805-811)
  g. Name of the clone from the cDNA library you have annotated that corresponds to the protein you have modeled. (e.g. Clone 20XY23.10)
  h. A blast2 sequence alignment between the your protein and the protein that was used to determine the structure you are modeling
  i. A description of the function of the protein you have modeled. What does the protein do in the cell or organism (e.g. glycolysis, protein translation, etc.)? Does it have a specific enzymatic activity (e.g. kinase, nuclease, etc)? What other proteins may it interact with? When is it likely expressed (e.g. in all cells all the time, just a subset of cells at specific times during development, etc)?
  j. A description of the color scheme you have used - including features you have highlighted. This may be a color scheme that: indicates identical or similar residues as predicted by the sequence alignments; the active site of the protein; structural components such as alpha helices and beta-strands; etc. If the protein sequence from the database is strongly conserved with your protein, you may want to highlight the differences.
2. JMol .jpg Script file (e.g. 1A3N.jpg)
3. Protein Data Bank (PDB) file (e.g. 1A3N.pdb or 1A3N.txt if you modified the file and used that to make your model)
4. A copy (.pdf) of the paper that used

To get started: A video of how to get started is here.

1. Students who have identified a clone from the cDNA library that codes for a full or partial protein should first search if a structure of a homologous protein has been determined by x-ray crystallography of NMR. This can be done by performing a NCBI BLASTP search with the predicted protein sequence from their clone and then examining if any of the matches that were identified in the Conserved Domain Database (CDD) contain structures (see lecture notes on CDD). Alternatively the students can search the Protein Data Bank (PDB) for the structure.

2. Perform a BLAST2 sequences alignment between the predicted protein sequence from the Wolffia clone and the protein sequence of the protein you will be modeling. This alignment is helpful to identify conserved residues on the structure model.

3. Download the pdb file (e.g. 1A3N.pdb) with the coordinates of the protein structure and use a version of the Download Jmol program that has been designed to create the physical models using Rapid Prototyping technology.  Zincfinger.pdb

4. Students should use the commands in Jmol to create a script file that will display the protein using the format features (spacefill, backbone, etc) and the colors they prefer. A color scheme may be used that indicates identical or similar residues as predicted by the sequence alignments; the active site of the protein; etc. If the protein sequence from the database is strongly conserved with your protein, you may want to highlight the differences. Please do not just highlight the helices and strands- this does not tell us much about the protein.

Note: Cartoons and strands don't build well.  Backbone, Wireframe and Spacefill work well (see sizes below).  Spacefill doesn't really show the protein structure well, just the overall shape.  It depends on what you are trying to show.  A typical structure may show a backbone model with few selected sidechains in ball and stick.  

Standard sizes that build well:
Backbone 1.5
Wireframe 1.0
Spacefill 1.25
hbonds 1.0
Struts 1.0

The commands wireframe and spacefill combined give a ball and stick.

Also, it is important when doing sidechains to use the command:
select *** and (sidechain or alpha)
where *** is the amino acid number
Otherwise you get a bumpy backbone.

There's a new tutorial at: http://cbm.msoe.edu/stupro/crest/resources.html (only available in IE).  It covers all the important information for building a model.

Jmol Training Guide - Below are resources to help with creating a model using RasMol. The RasMol Training Guide was developed by Shannon Colton at the Center for BioMolecular Modeling. Additional information can be found on the CBM JMol Resource Page

Jmol Color Guide: This provides a quick reference to the color options commands you may need to use in developing a Jmol image.