Hi all,
Professor Benoit Roux from the University of Chicago will be visiting
Harvard next Tuesday afternoon (03/03) for the Theochem lecture series
Please let me know if you're interesting in a half hour or an hour meeting
with him. We have spots available for dinner as well.
He will be giving the Theochem lecture on Wednesday (03/04) at MIT room
4-163. The talk title and abstract are below.
Thanks,
-Martin
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Martin Blood-Forsythe
Graduate Student in Physics
Harvard University
Aspuru-Guzik Lab
*"Membrane Potential And Small Charge Movement In Membrane Protein Systems"*
03/04/15 4:00PM MIT Building 4, Room 163
Benoit Roux
University of Chicago
Abstract:
A theoretical framework is elaborated to account for the effect of a
transmembrane potential in explicit solvent computer simulations of
membrane proteins [1]. The framework relies on a modified Poisson-Boltzmann
equation previously developed from statistical mechanical considerations
[2]. It is shown that a simulation with a constant external electric field
applied in the direction normal to the membrane is equivalent to the
influence of surrounding infinite baths maintained to a voltage difference
via ion-exchanging electrodes connected to an electromotive force. It is
also shown that the linearly-weighted displacement charge within the
simulation system tracks the net flow of charge through the external
circuit comprising the electromotive force and the electrodes. Using a
statistical mechanical reduction of the degrees of freedom of the external
system, three distinct theoretical routes are formulated and examined for
the purpose of characterizing the free energy of a protein embedded in a
membrane that is submitted to a voltage difference: the W-route constructed
from the variations in the voltage-dependent potential of mean force along
a reaction path connecting two conformations of the protein, the Q-route
based on the average displacement charge as a function of the conformation
of the protein, and the G-route based on the relative charging free energy
of specific residues, with and without applied membrane potentials. The
theory is applied to examine atomic models of the Kv1.2 potassium channel
in the active and resting state [2]. Methodologies to treat asymmetric
membrane conditions have also been developed [3]. Calculations of the
fractional transmembrane potential, acting upon key charged residues of the
voltage sensing domain of the Kv1.2 potassium channel, reveals that the
applied field varies rapidly over a narrow region of 10 to 15 Angstroms,
corresponding to the outer leaflet of the bilayer [4]. The focused field
allows the transfer of a large gating charge without translocation of S4
across the membrane. The theory is also applied to examine the binding of
sodium and potassium ions to the Na,K ATPase membrane pump.
1. B. Roux. Influence of the membrane potential on the free energy of an
intrinsic protein. Biophysical Journal. 1997;73(6):2980-9.
2. B. Roux. The membrane potential and its representation by a constant
electric field in computer simulations. Biophys J. 2008;95(9):4205-16.
3. F. Khalili-Araghi, B. Ziervogel, J.C. Gumbart, B. Roux. Molecular
dynamics simulations of membrane proteins under asymmetric ionic
concentrations. J Gen Physiol. 2013;142(4):465-75.
4. F. Khalili-Araghi, V. Jogini, V. Yarov-Yarovoy, E. Tajkhorshid, B. Roux,
K. Schulten. Calculation of the gating charge for the Kv1.2
voltage-activated potassium channel. Biophys J. 2010;98(10):2189-98.
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