BIOPHYSICAL THEORY AND MODELING |
The Interaction of Phospholipase A2 with a Phospholipid Bilayer: Coarse-Grained Molecular Dynamics Simulations
Chze-Ling Wee 1, Kia Balali-Mood 1, David Gavaghan 1 and Mark S.P. Sansom 1*
1 University of Oxford
* To whom correspondence should be addressed. E-mail: mark.sansom{at}bioch.ox.ac.uk.
Submitted on October 2, 2007
Revised on November 4, 2007
Accepted on 18 April 2008
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Abstract |
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A number of membrane-active enzymes act in a complex environment formed by the interface between a lipid bilayer and bulk water. Whilst X-ray diffraction studies yield structures of isolated enzyme molecules, a detailed characterisation of their interactions with the interface requires a measure of how deeply such a membrane-associated protein penetrates into a lipid bilayer. Here, we apply coarse-grained molecular dynamics (CG-MD) simulations to probe the interaction of porcine pancreatic phospholipase A2 (PLA2) with a lipid bilayer containing palmitoyl-oleoyl-phosphatidyl choline (POPC) and palmitoyl-oleoyl-phosphatidyl glycerol (POPG) molecules. We also used a configuration from a CG-MD trajectory to initiate two atomistic MD (AT-MD) simulations. The results of the CG and AT simulations are evaluated by comparison with available experimental data. The membrane-binding surface of PLA2 consists of a patch of hydrophobic residues surrounded by polar and basic residues. We show this proposed footprint interacts preferentially with the anionic headgroups of the POPG molecules. Thus, both electrostatic and hydrophobic interactions determine the location of PLA2 relative to the bilayer. From a general perspective, this study demonstrates that CG-MD simulations may be used to reveal the orientation and location of a membrane-surface bound protein relative to a lipid bilayer, which may subsequently be refined by AT-MD simulations to probe more detailed interactions.
Key Words:
coarse grained, membrane protein, molecular dynamics, phospholipase, simulation
