||August 1, 2011
||Dr. Zenmei Ohkubo, University of Illinois at Urbana-Champaign
||Spontaneous Binding and Insertion of Membrane-Anchoring Proteins Captured by a Highly Mobile Membrane Mimetic (HMMM) Model
Characterizing atomic details of membrane binding of peripheral membrane proteins by molecular dynamics (MD) has been seriously hindered by the slow dynamics of membrane reorganization associated with the phenomena. Consequently, the resulting structures are largely biased by the initial configuration of the lipids and proteins in the simulation system. To expedite lateral diffusion of lipid molecules and to accelerate formation of the optimal interaction between peripheral proteins and lipid headgroups during MD simulations, we have developed a highly mobile membrane mimetic (HMMM) model.
The HMMM model is composed of an organic solvent layer as the hydrophobic core sandwiched by water and with short-tailed phospholipids at the interface whose acyl tails are immersed in the organic phase. This configuration is formed spontaneously and rapidly, regardless of the initial position or orientation of the short-tailed lipids. The short-tailed lipids in the HMMM model exhibit about two orders of magnitude larger lateral diffusion than full lipids in conventional membrane models, whereas the membrane profile of the HMMM model is essentially the same as those of the full-membrane models.
As a challenging test of membrane binding of a peripheral protein without any guide, the GLA domain of human coagulation factor FVII was initially placed in bulk water in the HMMM model to simulate. During the MD simulation, the GLA domain inserted itself into the membrane spontaneously and reproducibly, with interactions closely matching those obtained previously using full membranes.
The HMMM model is extremely efficient in capturing the mechanism of membrane binding of a wide spectrum of peripheral proteins, as well as other membrane-associated phenomena.