It is worth noting that in the successful MD runs started from flat conformations of the peptides and resulting in apolar mode (especially in the case of DOPC/DOPG bilayer), an increase of bend-state population was more pronounced and associated with the insertion process (Figure , Supporting Information). MD analysis provided insights into the conformational space of the peptides in water, their hydrophobic surface behavior, and the relationship between these features and their biological properties. Multiple independent MD calculations in an aqueous environment showed conformational variability of all tested peptides, which is consistent with the NMR data obtained for p1, p3 and 15c. In set 2, the least toxic lead peptides (15c and 16c) were also found to be less flexible compared to the parent p3. At the same time, the more stable peptides, 5a and 13c, exhibited higher toxicity than their flexible parent peptides. Additionally, increased flexibility observed for the highly hemolytic peptides 8a and 8c -full D-analogues of p1 and p3 -suggests that flexibility may contribute significantly to peptide toxicity.