Scientific 3D animation of bump hole example

“Powering the Cell: mitochondria” and the “Inner Life of the Cell”, videos produced and distributed by XVIVO, are two of the most sensational examples of modern scientific animation.  An ensuing story in the New York Times solidified for me that scientific animation was not only a blooming industry producing eye candy for fund raisers but was also an active area of research and the beginnings of a community trying to push the boundaries of scientific communication.  This inspired me to get a copy of Maya (an industry-leading 3D animation software package freely available to the academic community) and get playing.

Even with all the inspiration from personal heroes Gael McGill and Drew Barry, the short animation above was the most style I could muster with my feeble newbie maya skills. The subject of this video is a particular example of the bump hole method, pioneered by Kevan Shokat [paper], which in general refers to the strategy of introducing a genetic mutation to a native enzyme in such a way that the enzyme can catalyze a specific reaction between the native substrate and another molecule.  In this case, the lab at Memorial Sloan Kettering Cancer Center (MSKCC) at whose request I made this video used the bump hole method to enable a transferase reaction that could attach a label to a substrate.  For a more detailed narrative of the video, please see the end of the post.

The stated purpose of this animation was to replace a simple 2D schematic illustration of the entire problem and its solution.  The video is intended to accompany a live presenter that will narrate the video.  Its primary function as a schematic allows us flexibility to deviate from scientific accuracy, when necessary.  The scientific accuracy here is limited to the shape of the molecules and the positioning of the substrate and cofactor relative to the enzyme.  All colors (obviously), transparencies and glow effects are for illustration.  Furthermore, the magnitude of the mutation’s effect on the enzyme geometry is greatly exaggerated to clearly show a perceptible change in the enzyme structure.  Walking the line between scientific representation and interpretation is something all scientific animators will have to deal with, and the rules for scientific integrity and responsibility in this arena are still up for discussion.  I hope that here I don’t exemplify any egregious violation.

A few tidbits for the interested.  I used the free and brilliant maya plugin for molecular animators called molecularMaya. As far as I understand, molecularMaya is the brainchild of Digizyme owner Gael McGill (and his super friendly and helpful team).  It allows for automatic importing of pdb files from the pdb website or locally on your machine.  The plugin provides a set of menu options for viewing the protein as a set of atoms, a mesh, or ribbon.  Each viewing mode is coupled to different style options.  For example, I used a mesh resolution of 1.714 for the enzyme to show more detail.  The mesh resolution does not,  as far as I am aware, translate to an Angstrom resolution.  molecularMaya is due for a much anticipated new release and I believe it will be significantly more than just a few new features.  One feature that I would really like would be the ability to select individual residues.  I trust additional representations such as beta-sheet and alpha-helix cartoons wil be included.

I hope to extend the utility of this animation with interactive labels and overlaid figures to supplement the content with scientific evidence.  In a dream world, scientisits will be communicating with each other and to the public through such interactive media. I expect also that 3D animations can be a valuable part of that media experience.  New presentation modalities are here and new ways of learning need to be explored.  We might as well also have some fun with it.

I apologize in advance for the generics, but the specific names and information about the enzymes, substrates, cofactors and mutations are privileged until publication.  The characters of this animation include a ‘blue’ enzyme, a ‘red’ substrate, and a ball-and-stick model of a cofactor that consists of a base and a clickable moiety, which I’ll refer to as the tag finger.

Scene 1 begins with an introduction to the native enzyme and its substrate.  Scene 2 introduces the cofactor and its constituent parts. Scene 3 consists of a demonstration of the problem, which is that the full cofactor does not bind to the native enzyme.  We tried to use the effect of the cofactor bouncing off the enzyme to clearly illustrate that the cofactor does not fit.  Scene 3 continues with the placement of the cofactor in its intended position.  Here we use a simple rotation to get a better view and a transparency on the enzyme mesh to give the viewer an idea of where the cofactor sits relative to the native enzyme. As the transparency goes away and returns to opaque, we see that the cofactor’s tag finger is no longer visible. We hope this clearly suggests that this part of the cofactor doesn’t fit the native enzyme structure.  Scene 3 concludes with a slow morph from a representation of the native enzyme into a representation of the mutated enzyme.  This part should conceptually explain that the effect of the mutation is to ‘make room’ for the cofactor tag finger.  In this part of scene 3 we take an artistic license and devaite from scientific accuracy.  We exaggerate the size of the hole, since at that mesh resolution, the deleted residue would be noticed.  Scene 4 shows the consecutive binding of the substrate and cofactor to the enzyme followed by an artistic (non-scientifically accurate) representation of the reaction carried out by the transferase, where the tag finger breaks from the cofactor and attaches to a specific lysine residue on the substrate.  I use a glow effect to represent the start of the reaction; Why? Scientists love glow effects, don’t we?  Scene 5 is the money shot.  It shows the individual components breaking off after the reaction, with special emphasis on the newly tagged substrate.