A recently developed software has been used to model peptides at a cytoplasm/membrane mimetic environment where the interface is represented by a discontinuity in the dielectric constant. Molecular dynamics and energy minimization procedures available in the program were applied to a wild type and to a 50% active mutant (Delta 78r(1)) peptide signal sequence of a lambda E. coli receptor (maltoporin). Modeling has been performed for both random coiled and constrained helical structures. As a general feature, the presence of the dielectric discontinuity induced the movement of the molecules’ center of mass toward the interface. A decrease in the energy along interface crossing (from epsilon = 80 to epsilon = 2) was observed and interpreted as an indication of their affinity for the lipid-mimetic phase. Distinct patterns of migration were recognized for each sequence, as well as in different simulated conditions for a same peptide. The random coiled peptides easily cross the interface, showing a tendency to go into the nonpolar phase, whereas constrained helical sequences tend to stay at the interface. Potential barriers and potential wells were identified in the modeling space for constrained helical peptides, which have been shown to be dependent on the peptide primary sequence, on the conformational restrictions imposed, and on the charge state of the peptide terminals.