Osh4 is an oxysterol binding protein (OSBP) homologue found in yeast that has been implicated in the intracellular transport of sterols between membranes. It has been proposed that Osh4 acts as a lipid transport protein, capable of transferring a single sterol residue from the endoplasmic reticulum to the plasma membrane. Phosphoinositides (PIPs) are thought to bind to Osh4's surface and play a key role in this proteins functionality.Blind docking techniques were used to probe the Osh4 surface and identify potential binding conformations. Model ligand compounds for phosphatidylcholine (PC), phosphatidylserine (PS), and two PIP [PI(4,5)P2 and PI(3,4,5)P3] head groups were docked against several conformational snapshots of the Osh4 proteins surface to determine possible regions favorable to interactions with membrane lipids. The PIP models frequently docked to a lysine-rich region on an exposed portion of the proteins β-barrel (β-crease region).This surface, along with the front and distal binding surfaces proposed from experimental cross-linking studies, were aligned with the surface of model membranes. Three model membranes were used containing: 1. PC/PE lipids, 2. PC/PE lipids with one PI(4,5)P2 residue per leaflet, and 3. PS and PI(4,5)P2 lipids in addition to PC/PE lipids. Systems were simulated using molecular dynamics for hundreds of nanoseconds. The Osh4 protein bound to the membrane in all cases where acidic residues were present in the membrane. The Osh4 protein did not bind to the membrane with only PC/PE lipids over the course of ∼1μs of MD simulation. Additionally, the bound membrane/protein conformation was largely the same regardless of the starting orientation of Osh4. This conformation featured charge-charge interactions between the protein and the membrane on several surface loops surrounding the β-crease region, and was stabilized by penetration of a surface phenylalanine into the membranes hydrophobic core.