Molecular simulations of lipid mediated protein-protein interactions
Frédérick Jean-Marie de Meyer 1*, Maddalena Venturoli 1 and Berend Smit 2
1 CECAM
2 UC Berkeley
* To whom correspondence should be addressed. E-mail: frederick.demeyer{at}yahoo.com.
Submitted on October 25, 2007
Revised on December 11, 2007
Accepted on 3 April 2008
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Abstract |
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Recent experimental results revealed that lipid-mediated interactions due to hydrophobic forces may be important in determining the protein topology after insertion in the membrane, in regulating the protein activity, in protein aggregation and in signal transduction. To gain insight into the lipid-mediated interactions between two intrinsic membrane proteins, we developed a mesoscopic model of a lipid bilayer with embedded proteins, which we studied with dissipative particle dynamics. Our calculations of the potential of mean force (PMF) between transmembrane proteins show that hydrophobic forces drive long range protein-protein interactions whose nature depends on the length of the protein hydrophobic segment, on the three dimensional structure of the protein and on the properties of the lipid bilayer. To understand the nature of the computed PMFs, the concept of hydrophilic shielding is introduced. The observed protein interactions are interpreted as resulting from the dynamic reorganization of the system to maintain an optimal hydrophilic shielding of the protein and lipid hydrophobic parts, within the constraint of the flexibility of the components. Our results could lead to a better understanding of several membrane processes in which protein interactions are involved.
Key Words:
biological membrane, hydrophilic shielding, mesoscopic model, molecular dynamics, potential of mean force, protein-protein interactions
