Investigating and Modeling the Binding Mechanism between VK4-40 and D3 Receptor (2024)

Undergraduates: Jessica Sain, Macy Parmelee, Mohana Mishra

Faculty Advisor: Rachel Penton
Department: Psychology and Neuroscience

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VK4-40 is a novel partial agonist of the dopamine D3 receptor (D3R) that has shown greater efficacy than traditional D3R agonists and antagonists in attenuating cocaine self-administration. Using 3D printing technology, we aim to provide a visual representation of how VK4-40 interacts with the D3 G-protein coupled receptor and induces a conformational change. VK4-40’s mechanism of action was simulated using a combination of 3D printed material, clay, and magnets. Based on the literature, partial agonism of the D3R involves the rotation of Helix 5, which in turn twists Helix 6 inwards. The iterative process of model prototyping was used to optimize the movement of the model, including rotating gears and magnetic coupling of the G protein. This physical model can illustrate VK4-40’s dose-dependent reduction of cocaine intake and relapse to stakeholders, emphasizing its potential as a treatment for cocaine use disorder.