Amphipathic helices are key domains of peripheral membrane proteins, targeting specific membranes to enable proper protein function as well as changing the local topology and lipid dynamics of the membranes they bind. Here, we use extended all-atom molecular dynamics to study, in detail, the binding mechanism and conformation of the N-terminus of the lipid-transport protein Osh4 in yeast, that is, the amphipathic lipid-packing sensor (ALPS) motif. We identified two binding conformations: (i) a vertical one with the N-terminus of the peptide embedded into the hydrophobic core and (ii) a horizontal, and energetically favored, conformation in which the hydrophobic side chains of ALPS are fully embedded into the membrane hydrophobic core. From extensive analysis on 21 trajectories of 2 mu s each, we describe peptide binding in terms of the structural changes that both the peptide and the membrane undergo upon binding as well as energetics of this interaction. The membrane models in this study include a simple binary lipid mixture, with a neutral and a charged lipid (1,2-dioleoyl-sn-glycero-3-phosphocholine-1,2-dioleoyl-sn-glycero-3-phospho-L-serine) and complex mixtures with lipid compositions characteristic of two organelles in yeast (each with more than six lipid types and an accurate sterol content). Our conclusions are in agreement with available literature, showing that the ALPS peptide is more likely to bind membrane surfaces with packing defects and higher anionic character. In addition, we show that there is an interplay between ALPS binding an existing packing defect and creating or enhancing one as the peptide binds to the membrane, which was previously suggested in the literature.