Figure 2: Experimental partitioning free energy and average membrane orientation of maculatin.

(a) CD spectra of the titration of 30 μM maculatin wild type (WT) and mutants with 100 nm POPC LUVs, show that membrane binding is strong ΔGbinding=−4.6±0.8 kcal mol−1. Consistent with the experimental binding the simulations show that at the molecular-level membrane binding is concomitant with interfacial folding of the peptide into a surface-absorbed alpha helix. (b) Oriented CD spectra of WT maculatin in POPC bilayer stacks at 100% relative humidity is 50±15% TM-inserted (peptide-to-lipid ratio=1/30). The dashed lines show theoretical helical spectra for peptides aligned perfectly parallel (red) and perfectly perpendicular (blue) to the beam, corresponding to TM and surface-bound peptides, respectively.