(fold1-4 is practically absent in both peptides, Table , Supporting Information), notable differences appear at the level of spatial organization of their hydrophobic side chains. The flat state is weakly populated for p1 and becomes the dominant conformation for 7a (Table , Supporting Information). We also found a strong correlation between "flat" and "bend" conformations of the hydrophobic pattern and the range of the dihedral angle φ of Dip6 in p1 and 7a (Figure ). In the flat state, most of the peptides exhibit an increase in the overall solvent exposure of the backbone atoms of hydrophobic residues (Table , Supporting Information). As a result, the flat-organized hydrophobic region of a peptide may be less effective in deep membrane insertion due to the reduced complementarity of the peptide surface with the hydrophobic environment of the membrane. Indeed, in contrast to other peptides from set 1 (p1, 5a, 8a) that have low occupancy of flat conformations and high hemolytic action, 7a is obviously less cytotoxic (Figure and Table , Supporting Information). To elucidate the potential differences in membrane-binding properties of a pair of the peptides with the same sequence and single L/D substitution of Arg1, the parent peptide p1 and less cytotoxic 7a, a series of MD simulations in a water-membrane environment was performed. The model membrane mimicking the mammalian cells was represented by a DOPC lipid bilayer. In addition, MD simulation of peptide 7a was carried out in the presence of a twocomponent bilayer DOPC/DOPG (with a molar ratio of 7.5/2.5) mimicking a bacterial membrane.