Rhomboid intramembrane proteases are bound to lipid membranes, where they dock and cleave other transmembrane substrates. How the lipid membrane surrounding the protease impacts the conformational dynamics of the protease is essential to understand because it informs on the reaction coordinate of substrate binding. Atomistic molecular dynamics simulations allow us to probe protein motions and characterize the coupling between protein and lipids. Simulations performed here on GlpG, the rhomboid protease from Escherichia coli, indicate that the thickness of the lipid membrane close to GlpG depends on both the composition of the lipid membrane and the conformation of GlpG. Transient binding of a lipid headgroup at the active site of the protease, as observed in some of the simulations reported here, suggests that a lipid headgroup might compete with the substrate for access to the GlpG active site. Interactions identified between lipid headgroups and the protein influence the dynamics of lipid interactions close to the substrate-binding site. These observations suggest that the lipid membrane environment shapes the energy profile of the substrate-docking region of the enzyme reaction coordinate.