We used coarse-grained molecular dynamics simulations to examine the effects of transmembrane α-helical WALP peptides on the behavior of four-component lipid mixtures. These mixtures contain a high-melting temperature (high-Tm) lipid, a nanodomain-inducing low-Tm lipid, a macrodomain-inducing low-Tm lipid and cholesterol to model the outer leaflet of cell plasma membranes. In a series of simulations, we incrementally replace the nanodomain-inducing low-Tm lipid by the macrodomain-inducing low-Tm lipid and measure how lipid and phase properties are altered by the addition of WALPs of different length. Regardless of the ratio of the two low-Tm lipids, shorter WALPs increase domain size and all WALPs increase domain alignment between the two leaflets. These effects are smallest for the longest WALP tested, and increase with increasing WALP concentration. Thus, our simulations explain the experimental observation that WALPs induce macroscopic domains in otherwise nanodomain-forming lipid-only mixtures (unpublished). Since the cell plasma membrane contains a large fraction of transmembrane proteins, these findings link the behavior of lipid-only model membranes in vitro to phase behavior in vivo.