Adenylyl cyclase (AC) is an important messenger involved in G-protein-coupled-receptor signal transduction pathways, which is a well-known target for drug development. AC is regulated by activated stimulatory (Gxcexb1s) and inhibitory (Gxcexb1i) G proteins in the cytosol. Although experimental studies have shown that these Gxcexb1 subunits can stimulate or inhibit ACs function in a non-competitive way, it is not well understood what the difference is in their mode of action as both Gxcexb1 subunits appear structurally very similar in a non-lipidated state. However, a significant difference between Gxcexb1s and Gxcexb1i is that while Gxcexb1s does not require any lipidation in order to stimulate AC, N-terminal myristoylation is crucial for Gxcexb1is inhibitory function as AC is not inhibited by non-myristoylated Gxcexb1i. At present, only the conformation of the complex including Gxcexb1s and AC has been resolved via X-ray crystallography. Therefore, understanding the interaction between Gxcexb1i and AC is important as it will provide more insight into the unknown mechanism of AC regulation. This study demonstrates via classical molecular dynamics simulations that the myristoylated Gxcexb1i1 structure is able to interact with apo adenylyl cyclase type 5 in a way that causes inhibition of the catalytic function of the enzyme, suggesting that Gxcexb1 lipidation could play a crucial role in AC regulation and in regulating G protein function by affecting Gxcexb1is active conformation.