Insertion of the Ca²⁺-independent phospholipase A₂ into a phospholipid bilayer via coarse-grained and atomistic molecular dynamics simulations.

ABSTRACT: Group VI Ca²⁺-independent phospholipase A₂ (iPLA₂) is a water-soluble enzyme that is active when associated with phospholipid membranes. Despite its clear pharmaceutical relevance, no X-ray or NMR structural information is currently available for the iPLA₂ or its membrane complex. In this paper, we combine homology modeling with coarse-grained (CG) and all-atom (AA) molecular dynamics (MD) simulations to build structural models of iPLA₂ in association with a phospholipid bilayer. CG-MD simulations of the membrane insertion process were employed to provide a starting point for an atomistic description. Six AA-MD simulations were then conducted for 60 ns, starting from different initial CG structures, to refine the membrane complex. The resulting structures are shown to be consistent with ea

SUBMITTER: Bucher D 

PROVIDER: S-EPMC3723492 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature