We also tested the interactions between the Fibroblast growth factor II (FGF2) 101-103 , a PI(4,5)P2 binding protein , and a membrane with 5 mol% of PI(4,5)P2 in a POPC background. Like the above observations for the PH domain, FGF2 does not form a stable complex with the membrane over the 10 µs simulation (Figure ). Finally, we tested the viral protein 40 (VP40) dimer and PS lipid interactions in a membrane composed of 30 mol% POPS, and 30 mol% cholesterol in a POPC background. In previous CHARMM36m simulations, we observed and quantified the binding of the VP40 dimer with the membrane and successfully reproduced the interactions with experimentally known binding pockets, including K224, K225, K274, and K275 107 . Here, in Martini 3 simulations, while binding to the membrane was not an issue, achieving the correct orientation of the protein with the experimental binding residues facing the membrane was challenging. The choice of the initial system from which the protein was coarse-grained made a significant difference for the VP40 dimer. The best results were achieved by coarse-graining the protein from an atomistic model pre-bound to the membrane. In this configuration, the protein interacted with the membrane via the experimentally identified binding residues in ~90% of the frames where membrane interaction occurred (Figure , right panel).