Spatial Modelling

Spatial modelling

In order to get a sense for how to optimally assemble our reporter and detector molecules for integration with the prototype, we used Autodesk Maya to build and analyze potential capture protein fusions in silico. In contemplating the prototype design of capture TALE detectors in the nitrocellulose lateral flow strip prototype, the wetlab team conceived the following protein fusion designs:

We were concerned about how the interaction of TALE detectors with the nitrocellulose substrate might reduce their sensitivity. The wetlab asked the modelling team who proposed simulating the capture proteins and nitrocellulose in Maya to answer this question. In order to determine potential for steric hinderance issues with DNA binding, we needed to know how DNA and TALEs bind together. The steps in this interaction have not been previously documented, so we animated a putative interaction in Maya. See Figure 2 below.

The interaction between the TALE and DNA appears to require intricate contortions of the TALE and space around the periphery of the protein. The next step was to use Maya to show how the interaction of DNA with the TALE is influenced by association of the TALE with a surface such as nitrocellulose. See Figure 3 below.

In Figure 3A, the TALE is associated directly with a surface representing nitrocellulose, whereas in 3B, it is separated by linker sequence separating the TALE from the surface. Given the geometric constraints of the TALE-DNA interaction shown in Figure 2, the modelling team concluded that capture TALEs in the system should be bound to a protein to separate detector from nitrocellulose. From this data, the wetlab will be focussing prototype development where capture TALEs are fused to ferritin to separate them from nitrocellulose (see Figure 1B and 3B).

Animation of complete system

The Modelling team has been tasked with simulating the biological interactions of our proposed system at the nanoscale level using the Autodesk Maya animation software and Wolfram Mathematica. We have been able to accomplish our tasks towards our ultimate goal of creating a professional, compelling and useful animation for the competitions this fall. Although our qualitative work is presented as a video that lasts only a few seconds, the majority of our time this summer and fall was dedicated towards creating an animation that could be understood by a general audience.

The Maya platform is intended for advanced users to function efficiently although Autodesk has made this software generally usable for beginners. The learning curve is very steep, and we needed to ensure that the time we invested in learning more advanced techniques would serve as beneficial. Since the physics of our biological interactions have not yet been defined, we could not make use of the Maya physics engine to fully calculate the orientations and interaction of the molecules. This had required us initially to use the basic technique of 'key-framing' intervals, and sometimes to key sequential frames as well. In other words, we were required to manually rotate, translate, and scale our molecules individually to define initial and final states, so the Maya physics engine could seamlessly transition the molecule within the given time interval; or, we needed to define each sequential frame to create a sequence of images similar to an animated flip-book.

3D Printing:

Through our collaboration with Cesar Rodriguez, a Senior Research Scientist in the Bio/Nano/Programmable Matter group at Autodesk, we have been able to expand our spatial modelling beyond the computer screen. He and his team have offered us access to the 3D printing services at Autodesk to make a tangible model of our molecules based off of our Maya simulations. This has allowed our team to get a feel for the shape of our proteins, aiding the the design of our prototype, linkers, and the system as a whole.