Hey everyone, this will be a short post today with another planned to go live by the end of the week. I left off giving a sneak peek into the next modeling project I planned with BCR-ABL. This post will go over the process I went through to edit this structure in Fusion360.
Firstly, the STL files for BCR-ABL and Gleevec (Imatinib) were obtained from the link provided. Chronic myeloid leukemia (CML) is a cancer of white blood cells. In CML, white blood cells divide uncontrollably due to an overactive tyrosine kinase protein called BCR-ABL, which results from a chromosomal translocation. This chromosomal translocation creates what is known as the “Philadelphia chromosome.” Research into CML treatments has consisted of understanding the mechanisms of BCR-ABL. Since BCR-ABL is classified as a kinase enzyme there is an interaction with ATP. Researchers were able to understand that inhibition of ATP to BCR-ABL resulted in deactivation. This led to the production of Imatinib, an inhibitory drug that binds to BCR-ABL competitively with ATP.
Editing BCR-ABL in Fusion360
Since the mechanism of Imatinib binding with BCR-ABL involves a conformational change that locks the molecule inside BCR-ABL, I had to do a slightly different design for modeling the substrate binding. In this new design the model of BCR-ABL is split down the middle allowing for the model of Imatinib to be inserted in the substrate binding zone before closing the BCR-ABL model. The same process can be done with ATP to show the similar binding process.
This was completed by using the “Plane Cut” function. This can be found under the “Mesh” tab, subsection “Modify.” When using this command ensure that “Type” is set to split body and “Filly Type” is set to uniform.
Two cylindrical tubes were created at around a 50mm diameter (important for later) and positioned in areas that allow them to act as pegs when printed.
These cylindrical tubes underwent the “Tessellate” function (found in the “Mesh” tab, subsection “Create”) and subsequently the “Combine, cut” function (found in the “Mesh” tab, subsection “Modify”) was used with each half of the BCR-ABL model creating a hole for the peg (one for each half).
A new set of cylinders was created using the same process as before but at around a 48mm diameter. The diameter was reduced slightly as in the last print using pegs, I found it was too difficult to pull the model apart.
I decided to use the same stand that I created before since it looked quite nice, and I had no issues with it. The procedure for completing this process is outlined in one of my previous posts if you are interested.
This is an image of the final product. In my next post, which will go live either tonight or tomorrow tonight, I will go over the printing process for this model. The next post after that is my last post in this series 🙁 which will go over my final project in its entirety.