Mark J. Arcario, Y. Zenmei Ohkubo, and Emad Tajkhorshid.
Capturing spontaneous partitioning of peripheral proteins using a
biphasic membrane-mimetic model.
Journal of Physical Chemistry B, 115:7029-7037, 2011.
ARCA2011-ET
Membrane binding of peripheral proteins, mediated by specialized anchoring
domains, is a crucial step for their biological function. Computational studies of
membrane insertion, however, have proven challenging and largely inaccessible,
due to the time scales required for the complete description of the process, mainly
caused by the slow diffusion of the lipid molecules composing the membrane.
Furthermore, in many cases, the nature of the membrane ``anchor", i.e., the part
of the protein that inserts into the membrane, is also unknown. Here, we address
some of these issues by developing and employing a simplified representation of
the membrane by a biphasic solvent model which we demonstrate can be used
efficiently to capture and describe the process of hydrophobic insertion of
membrane anchoring domains in all-atom molecular dynamics simulations.
Applying the model, we have studied the insertion of the anchoring domain of a
coagulation protein (the GLA domain of human protein C), starting from multiple
initial configurations varying with regard to the initial orientation and height of the
protein with respect to the membrane. In addition to efficiently and consistently
identifying the ``keel" region as the hydrophobic membrane anchor, within a few
nanoseconds each configuration simulated showed a convergent height (2.20
1.04 Å) and angle with respect to the interface normal (23.37
12.48). We demonstrate that the model can produce the same results as
those obtained from a full representation of a membrane, in terms of both the
depth of penetration and the orientation of the protein in the final membrane-
bound form with an order of magnitude decrease in the required computational
time compared to previous models, allowing for a more exhaustive search for the
correct membrane-bound configuration.
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1.04 Å) and angle with respect to the interface normal (23.37 
). We demonstrate that the model can produce the same results as
those obtained from a full representation of a membrane, in terms of both the
depth of penetration and the orientation of the protein in the final membrane-
bound form with an order of magnitude decrease in the required computational
time compared to previous models, allowing for a more exhaustive search for the
correct membrane-bound configuration.
