Apalutamide and Androgen Receptor Therapy
Androgen agonist therapies, like Lupron, are used to treat metastatic prostate cancer however prolonged use can increase the risk of developing castration resistant prostate cancer (CRPC). Androgens testosterone and 5a-dihydrotestosterone (DHT) are responsible for driving the cancerous proliferative process. Apalutamide intersects the ligand binding domains of androgen receptors (AR) to act as a second level of defense against a CRPC.
Audience: Prostate cancer patients eligible for AR therapy.
Software: 3ds Max, Blender, VMD, and Adobe After Effects
Prior to modeling and scene development it was imperative to understand the conformational changes of all involved proteins and the relationships between domains. For instance an important characteristic of an androgen receptor is it’s long intrinsically disordered chain. When a ligand binds this chain folds to bind sequence “FQNLF” to the LBD.
To the right is a sample of my organization chart, below my storyboard. For my storyboard I depicted my AR receptor as a simplistic mechanism to more easily communicate the mechanism of action and the characters involved.
Pre - Production Phase
When working with molecular mechanisms of action accuracy is supported rather than eclipsed by my stylization. For instance rather than using an androgen receptors long disordered chain, a smaller chain was constructed to allow for a cleaner and more digestible animation.
A series of animation tests were necessary to grasp the cellular environment in which the AR receptor would reside in. In this test, link constraints were tested on cubes. Link constraints allow for an object to lock itself to another, a useful technique used for the androgens and Apalutamide.