NMP 2008
 |
Dan Bolintineanu |
ADVISOR:
Ted Davis and Yiannis Kaznessis |
Computer Simulations of a Peptide Nanopore in a Lipid Bilayer
Dan Bolintineanu, Allison Langham, and Yiannis Kaznessis
Protegrins are small, cationic antimicrobial peptides (AMPs) that are believed
to act against bacterial infections by compromising the integrity of the
bacterial cell membrane. Experimental evidence suggests that protegrins,
as well as other AMPs, act cooperatively to form nanoscale pore structures
that completely disrupt normal membrane function. We have conducted extensive,
fully atomistic molecular dynamics (MD) simulations of a protegrin pore in
a lipid bilayer to explore the molecular interactions and main structural
features of such pores. We have additionally used the simulations as input
to a continuum electrodiffusion analysis of ion permeation (commonly referred
to as Poisson-Nernst-Planck theory). The coupled steady-state Poisson-Nernst-Planck
equations are solved numerically, using the geometry, charge density, and
ion diffusivity profile obtained from the MD simulations. This multiscale
approach allows for a quantitative analysis of ion transport through a protegrin
pore in the biologically relevant non-equilibrium state (in particular, ion
transport in the presence of an applied field, or in the presence of a concentration
gradient). Results from this approach are shown to be in reasonable agreement
with previous experimental measurements of similar systems, in particular
conductance and ion selectivity measurements. The relatively low computational
cost of this approach allows us to explore numerous aspects of ion transport
through a protegrin pore, including current-voltage relationships, the relative
importance of geometry and charge distribution, ion types and diffusivities,
and external conditions.
Read Dan Bolintineanu's current CV.