Fig 1.
Helical wheel representation of LK and EALA.
Both peptides are designed to display secondary amphiphilicity when they adopt the α-helix conformation.
Fig 2.
Three separate contributions govern the dynamic conformational equilibrium of an amphiphilic peptide.
The folding of the individual molecule in solution (A); the partitioning of hydrophobic/hydrophilic residues induced by macroscopic interfaces (B) or molecular interfaces upon aggregation (C). Combinations of these effects (connecting arcs D, E and F) determine the preferred secondary structure in a given environment.
Fig 3.
Time evolution of secondary structure for LK (left) and EALA (right) when isolated in bulk water.
Snapshots depicting various conformations adopted by these molecules (A and B), DSSP analysis of secondary structure (C and D), SASA for hydrophobic sidechains (h-SASA), number of intra-peptide backbone hydrogen bonds (H-bond) and short-range Coulomb interaction energies (Coul-SR) between the charged groups (E and F) are given for both of the molecules. See Methods section for the color coding and representation of peptides in A and B.
Table 1.
Average short range Coulomb energy, hydrophobic SASA, and number of intra-mainchain hydrogen bonds for LK, AK and EALA.
Fig 4.
Simulations of a single peptide at the vacuum/water interface for LK (left) and EALA (right).
Simulations are started with random conformations at the center of the water slab. Upon adsorption of peptides (after 45 ns for LK and 50 ns for EALA) partitioning of hydrophobic/hydrophilic residues and folding into the α-helix structure (after 800 ns for LK and 350 ns for EALA) is observed. Snapshots depicting the adsorption and adoption of the α-helix structure (A and B) and the DSSP analysis of the secondary structure evolution (C and D) are shown for both molecules. SASA, intra-peptide backbone hydrogen bonds and short-range Coulomb interaction energies between the charge groups (E and F) display the partitioning of hydrophobic/hydrophilic residues and secondary structure formation in the presence of the interface.
Fig 5.
Time evolution of secondary structure of a single AK (in-silico mutated form of LK) peptide at the vacuum/water interface.
Initially the peptide is submerged in bulk water and moves to the interface in 80 ns and remains there for the rest of the simulation.
Fig 6.
Folding and association of a pair of LK (left) and EALA (right) peptides in bulk water.
Snapshots illustrating the aggregation process (A and B), DSSP secondary structure analysis (C and D), SASA, short range Coulombic interaction energies between the charged groups and the number of intra and inter-peptide backbone hydrogen bonds (E and F) are displayed as a function of simulation time. Association of peptides take place at 180 ns for LK and 300 ns for EALA, which can be observed via the sharp drop in SASA.
Fig 7.
PMF results comparing the separation of a LK dimer in bulk water for the cases where lysine residues are positively charged, lysine residues are neutral and the leucine residues are in silico mutated to alanine residues.
The curves are shifted so that the maximum points are zero. The distance refers to the distance between the center of mass of backbone atoms of the peptides. For the mutated AK dimer, when the peptides are in contact they maintain their helical structures. However when they are separated or when they make a loose contact the α-helical structure is not conserved.
Fig 8.
Time evolution of the secondary structure of a dimer of LK (left) and EALA (right) at the vacuum/water interface.
Typical snapshots when the peptides are associated at the interface (A and B), DSSP structural analysis (C and D), angle between the helix axis for the peptides and center-to-center distance (E and F), the h-SASA for each peptide along with the buried SASA for the whole peptide, the inter and intra molecular short-range Coulomb energies and the number of inter- and intra-molecular hydrogen bonds (G and H) are shown in figure.