Membrane builder

A special protocol was developed to assemble the starting configuration for MD simulations of membrane proteins associated with phospholipid bilayer membranes. The purpose of the protocol is to construct an initial configuration of a protein-membrane complex that is as close as possible to that of an equilibrated system. The construction method was developed by Woolf and Roux and applied to the simulation of the gramicidin A channel, pf1 coat protein, melittin and the KcsA potassium channel (Woolf and Roux, 1994; Woolf and Roux, 1996, Berneche et al., 1998; Berneche and Roux, 2000). This approach represents an extension of the work of Pastor and co-workers to investigate pure lipid bilayers (Pastor et al., 1991; Venable et al., 1993).
Our general strategy for creating a reasonable starting configuration for the protein phospholipid system consists in randomly selecting lipids from a pre-equilibrated and pre-hydrated set, placing them around the protein, and finally reducing the number of core-core overleaps between heavy atoms through systematic rotations (around the Z-axis) and translations (in the XY plane) of the lipids and protein. To provide the initial XY positions for each lipid, the full molecules are first represented as single effective particles corresponding to the average cross-section area of a single phospholipid. The packing of the effective lipid particles around the protein is determined from a MD simulation in which the large effective particles are harmonicaly restrained at a given value of Z and moving in the XY plane with periodic boundary conditions.