Membrane active peptides are excellent targets for MD simulations. They are smaller than membrane proteins, their behavior is highly sensitive to lipid composition, and they are difficult to study experimentally. This increases the chances that a simulation will be well-converged, interesting, and useful. The results of multi-microsecond simulations of the antimicrobial peptide (AMP) piscidin 1, a model nascent high density lipoprotein (HDL) particle, and apolipoprotein mimetic peptides on a HDL-sized lipid nanodisc are described.  Simulations of the AMP piscidin 1 in preformed pores and surface bound states strongly indicated that pores are not stable, and support a “transient defect” model of membrane disruption by AMPs. Simulations of nascent HDL highlight the flexibility of apolipoproteins: the N-terminal of one ApoA-1 migrated from the edge to the top of the disc and interacted directly with the lipid head groups; images from negative stain tomography reconstruction show similar features. Simulations of two different ApoA-1 mimetics indicated a preference for a double belt (like ApoA-1 on nascent HDL), rather than a “picket fence” arrangement, and showed clear differences in stability between the peptides. <br/>

Microsecond simulations of antimicrobial peptides and mimetics of ApoA-I

254th National Meeting (2017)

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