We calculated the minimum distance between the protein and membrane, with focus on two important membrane binding residues , Lys44 and Tyr246. For the DMPC system, we ran five independent 1 μs-long simulations, where we did not observe stable binding at the known protein-lipid interface (Figure ). Five more independent 5 μs-long simulations were carried out to test if the timescale of the simulations could impact binding: We retrieved a similar trend (Figure ), with some simulations showing a rolling motion of the protein on the membrane surface. In contrast, simulations performed with POPC lipids did retrieve the binding of the protein to the membrane with the right orientation (Figure ,C), with binding persisting over the timescale of the simulations (Figure ). Even when binding to the membrane occurs through the wrong interface, the protein reorients and binds with the right orientation (Figure ). The different results obtained from the DMPC and POPC simulations highlight the tightness of the DMPC membrane, possibly linked to the slight decrease in APL (Figure ). This highlights the impact of membrane composition on protein binding, and how it may affect membrane penetrating residues, proteins, or peptides.