Animated GIF's, such as the small moving images at right, can be created with help from Protein Explorer -- see Making an Animated GIF File with Protein Explorer.
 

Animations of conformational changes show interpolations or "morphs" between two experimentally observed conformations. They help the eye to relate the two conformations, but rarely if ever do they attempt accurately to predict the true trajectory of a reaction. The rationale and limitations of protein morphs are summarized at the Protein Morpher.

The "canned" animation, above left, can be rotated (by dragging on it with your mouse), but is limited to one rendering and color scheme. When the animation is played in Protein Explorer, you can view it in a variety of renderings (secondary structure cartoon, ball and stick, spacefilling) and color schemes. Also, the playback speed can be adjusted, or each frame can be viewed individually.

Once you obtain an animation that can be played in Protein Explorer, you can save the animation window directly from Protein Explorer as HTML. It can then be played back in Netscape (smoother animation) or Internet Explorer (jumpier animation) without running Protein Explorer. For example, here is such a saved animation HTML file (press the Animate button to start animation) for serotonin N-acetyltransferase binding substrate.

Starting Animation in Protein Explorer The links on this page automatically start Protein Explorer at the NMR Models/Animation page (Note 2). All you have to do is wait for the green "Ready" indicator, and press the [Animate] button. Important - READ THIS When loading ensembles of NMR models or morphs elsewhere, Protein Explorer will likely default to starting at the FirstView page. To start animation: Scroll down to the bottom of the FirstView control panel, and click on PE Site Map. In the PE Site Map, click on NMR Models/Animation. Press the [Animate] button. Try the EF Hand this way.

Here are links that show examples of morphs in Protein Explorer. See the yellow box at left for instructions.

1. The EF hand shown on this page, binding calcium (from recoverin). Replace the default script in the box on Protein Explorer's NMR Models/Animation page with this script, and then press the [Animate] button.

2. Recoverin expelling N-terminal myristic acid upon binding calcium. Caution: this is a linear interpolation. For a full explanation of the limitations of linear interpolation and an introduction to recoverin, see the Protein Morpher. It includes only alpha carbons -- hence, trace, cartoon, and secondary structure colors cannot be displayed. (1iku model 7 -> 1jsa model 9.)
    
   
3. Lac repressor bending the DNA operon as it goes from nonspecific DNA binding to specfic sequence recognition. Several saved animations are available highlighting different aspects.
    
   
4. The bacterial flagellar hook: a molecular universal joint. Several saved animations and a morph illustrate different aspects of this movement.

5. Calmodulin binding peptide. Caution: this is a linear interpolation. For a full explanation of the limitations of linear interpolation and an introduction to recoverin, see the Protein Morpher. Although calcium ions remain bound at all times, for technical reasons, they are shown only in the two end states. This morph includes only alpha carbons -- hence, trace, cartoon, and secondary structure colors cannot be displayed. (1osa -> 2bbm.)
   To see the position of the peptide throughout the morph, insert the two commands below in the script box, immediately before the line "#--End color scheme--".
   select :b
   dots 20
   #--End color scheme--

4.   Serotonin N-Acetyl transferase binding inhibitory substrate analog. This enzyme catalyses the penultimate but rate-limiting step in melatonin synthesis. Caution: this is a linear interpolation. For a full explanation of the limitations of linear interpolation and an introduction to recoverin, see the Protein Morpher. This morph includes only alpha carbons -- hence, trace, cartoon, and secondary structure colors cannot be displayed, but this speeds up the animation considerably. Here is the same animation with all sidechains (generated by the Morph Server of Krebs and Gerstein). (1b6b:a -> 1cjw:a) To see the position of the substrate throughout the animation, insert these two commands as instructed in the previous paragraph.
   select ligand
   dots 30

   To highlight sidechains with dramatic movements, delete the script in the box and paste this script in, then press Animate.  

5. Staphylococcal accessory regulator A (SARA) binding DNA. This is a transcriptional regulator controlling virulence (Schumacher et al., 2001). Caution: this is a linear interpolation. For a full explanation of the limitations of linear interpolation and an introduction to recoverin, see the Protein Morpher. This morph includes only alpha carbons -- hence, trace, cartoon, and secondary structure colors cannot be displayed, but this speeds up the animation considerably. Doing a morph with sidechains is problematic because a homodimer is required, and each monomer contains gaps. (1fzn dimer from PQS -> 1fzp) To see the position of the DNA throughout the animation, insert the two commands below in the script box, immediately before the line "#--End color scheme--".
   select dna,hetero
   dots 30
   #--End color scheme--
    

6. Lipase (triacylglycerol hydrolase) has been observed in both closed and open conformations (Grochulski et al., 1994). This transition starts with the catalytic site "closed" and the enzyme surface largely polar, so the protein is likely soluble. A single loop moves to open access to the catalytic site, leaving a hydrophobic pocket, presumably able to engage a substrate fat droplet. Caution: this is a linear interpolation. For a full explanation of the limitations of linear interpolation and an introduction to recoverin, see the Protein Morpher. This morph includes only alpha carbons -- hence, trace, cartoon, and secondary structure colors cannot be displayed, but this speeds up the animation considerably. (1trh -> 1lpm; thanks to Byron Rubin for acquainting me with lipase.) To see the position of the inhibitor (substrate analog) throughout the animation, insert the two commands below in the script box, immediately before the line "#--End color scheme--".
   select mpa
   dots
   #--End color scheme--

1. The process of HIV protease inhibitor Ritonavir binding to the protease has been simulated, starting with 1HXW, by pulling the inhibitor out of the "side" of the protease with concurrent real-time energy minimization by molecular mechanics using MDL Sculpt. This simulation is fictional, but chemically possible. Here are four animations saved from Protein Explorer's NMR/Animations page, emphasizing backbone, spacefill, contacts, or water. You can also view the animation in PE, where you can control the rendering and color scheme. Here are the scripts that produced the renderings and colorings in the previous four saved animations. Here is an alternative simulation in which the inhibitor was pulled out the "top" of the protease, opening the "lid".

   

2. Water assembling into a hydrogen-bonded network: Simulation with 10 water molecules.

When ensembles of models resulting from NMR experiments are animated, they simulate thermal motion. Here are some examples.

1. Recoverin (1JSA), N-terminus flexible with covalently linked myristic acid. To speed up the animation, this link shows only the alpha carbons, but that precludes rendering as cartoon, trace, or spacefill. Alternatively, being aware that it is a large file (1.1 megabytes), here is the ensemble of NMR models with all sidechains.  

2. Calmodulin (1CFC), calcium-free form, much flexibility. To speed up the animation, this link shows only the alpha carbons, but that precludes rendering as cartoon, trace, or spacefill. Alternatively, being aware that it is a large file (1.1 megabytes), here is the ensemble of NMR models with all sidechains.

3. Calmodulin (2BBN), calcium-bound form, little flexibility. To speed up the animation, this link shows only the alpha carbons, but that precludes rendering as cartoon, trace, or spacefill. Alternatively, being aware that it is a large file (1 megabyte), here is the ensemble of NMR models with all sidechains.