To gain insights into the principles that govern the action of antimicrobial and cell penetration peptides, we use molecular simulations to study the self-assembly behaviors of cationic peptides and lipid mixtures. Specifically, we use a coarse-grained model recently developed in our group, the BMW-MARTINI force field; this model pays particular attention to the treatment of electrostatic interactions and therefore is well suited for describing the complex interactions among highly charged peptides, water, ions and lipid mixtures, while maintaining great computational efficiency. Motivated specifically by the recent studies of Wong and co-workers, we compare the self-assembly behaviors of lipids with cationic peptides that include either Arg residues or a combination of Lys and hydrophobic residues; in particular, we attempt to reveal factors that stabilize the cubic ``double diamond' Pn3m phase over the inverted hexagonal H$_{II}$ phase. For example, to explicitly test the importance of the bidentate hydrogen-bonding capability of Arg to the stabilization of negative Gaussian curvature, we also compare results using variants of the BMW-MARTINI model that treat the side chain of Arg with different levels of details. Collectively, the results suggest that both the bidentate feature of Arg and the overall electrostatic properties of cationic peptides are important to the self-assembly behavior of these peptides with lipids. The results are expected to have general implications to the mechanism of peptides and proteins that stimulate pore formation in biomembranes.

Self-assembly of cationic peptides and lipid mixtures: Mechanistic insights from simulations using a new coarse-grained model

244th National Meeting (2012)

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