BIOPHYSICAL THEORY AND MODELING |
Molecular Dynamics Simulation Studies of the Effect of
Phosophocitrate on Crystal Induced Membranolysis
Pranav Dalal 1, Kimberly Zannotti 1, Andrzej Wierzbicki 2*, Jeffry D Madura 1 and Herman S Cheung 3
1 Duquesne University
2 University of South Alabama
3 University of Miami
* To whom correspondence should be addressed. E-mail: awierzbi{at}jaguar1.usouthal.edu.
Submitted on December 21, 2004
Revised on January 29, 2005
Accepted on 1 July 2005
 |
Abstract |
|---|
In this study, following our earlier work on Calcium Pyrophosphate Dihydrate (CPPD) crystal-induced membranolysis (Wierzbicki et al., 2003) we demonstrate, using the CHARMM method of molecular dynamics simulation, the protective role of phosphocitrate (PC) against solvated Dimirystoyl phosphatiadylcholine (DMPC) phospholipid bilayer disintegration on contact with the CPPD crystal. Our molecular dynamics simulations studies show that coverage of the CPPD crystal with a layer of phosphocitrate molecules results in the conservation of phospholipid bilayer integrity. We show that the rupture of the lipid bilayer in presence of CPPD and the protective effect of PC is primarily due to electrostatic interactions. The protective role of phosphocitrate, which may also play an important and potentially therapeutic function against crystal-induced membranolysis is also discussed.
Key Words:
Inhibitory effect, Lipid rupture, Molecular dynamics, Pseudogout
