Insulin plays a crucial role in regulating glucose levels in higher organisms. The way insulin binds to its receptor and activates signal transduction is of particular interest. Experimental studies have revealed that insulin has two distinct binding sites on the extracellular portion of the insulin receptor (IR) suggesting the coexistence of high and low affinity (negative cooperativity) binding sites1, 2, 3. A significant recent breakthrough has been the determination of the crystal structure of the IR-insulin complex4. We have used this new crystal structure information to perform molecular dynamics simulations to characterise the primary binding site by identifying the strongly interacting residues. Our preliminary results, which corroborate the experimental data, suggesting the direct interaction of insulin with the IR carboxy terminal α-chain (αCT) segment and restricted contact between insulin and the first leucine-rich repeat domain (L1) of the IR4, 6. Furthermore, structural changes occur both within insulin and the receptor. Specifically, insulin undergoes a conformational switch upon binding to the IR which is consistent with recent studies4, 5.