(65a) Molecular Dynamics Simulations of Lipid-Protein Interactions

We use atomistic and coarse-grain simulations to reveal details of interactions of short peptides, such as lung surfactant peptides and antimicrobial peptides with lipid monolayers and bilayers. The insertion of these peptides into the lipid layers, and the position and orientation angles selected by these peptides are investigated and compared with available experimental data. In general, there are multiple, rapidly fluctuating, hydrogen-bonding interactions between the positively charged residues of the peptides and negatively charged lipid head groups that affect peptide position and orientation and greatly slow the equilibration. Insertion and pore formation can be accelerated in the presence of an electrostatic potential produced for example by counterion imbalance. We also investigate ?hydrophobic mismatch? in the length of hydrophobic domains of transmembrane peptides relative to the width of the hydrophobic domain of bilayers using model ?KALP? peptides consisting of alanine and leucine lipophilic residues capped at both ends by lysines. We find that the peptide/bilayer system compensates for mismatch through a combination of peptide tilting, local bilayer bending, and lysine side-chain ?snorkeling,? in the case that the hydrophobic domain of the peptide is shorter than that of the lipid bilayer. Some of these phenomena can be captured by coarse-grained models that are orders of magnitude faster than atomistic simulations and can reach times of microseconds on fast processors.