Monotopic proteins make up a class of membrane proteins that bind tightly to, but do not span, cell membranes. We examine and compare how two monotopic proteins, monoamine oxidase B (MAO-B) and cyclooxygenase-2 (COX-2), interact with a phospholipid bilayer using molecular dynamics simulations. Both enzymes form between three and seven hydrogen bonds with the bilayer in our simulations with basic side chains accounting for the majority of these interactions. By analyzing lipid order parameters, we show that, to a first approximation, COX-2 disrupts only the upper leaflet of the bilayer. In contrast, the top and bottom halves of the lipid tails surrounding MAO-B are more and less ordered, respectively, than in the absence of the protein. Finally, we identify which residues are important in binding individual phospholipids by counting the number and type of lipid atoms that come close to each amino acid residue. The existing models that explain how these proteins bind to bilayers were proposed following inspection of the X-ray crystallographic structures. Our results support these models and suggest that basic residues contribute significantly to the binding of these monotopic proteins to bilayers through the formation of hydrogen bonds with phospholipids.