SCIENCE AT THE EDGE SEMINAR SERIES

Quantum Biology / Gene Expression in Development and Disease Seminar

Friday, 14 October 2011 at 11:30am

Room 1400 Biomedical and Physical Sciences Bldg.

Refreshments at 11:15

Speaker: Rob D. Coalson
         Department of Chemistry, University of Pittsburgh

Title:   Modeling Permeation through Biological Ion Channels:
         A Physico-Chemical Perspective

Abstract:

Ion channel proteins embed in the cell membrane so as to establish a
membrane spanning aqueous pore.  Most ion channels undergo conformational
changes, induced by precise physiological stimuli, between a configuration
which allows ions to flow through the aqueous pore (the 'open' state) and
one that prevents such flow (the 'closed' state).  It is challenging to
compute, from basic physico-chemical principles, the current of ions that
flows down the electrochemical gradient presented to them when the channel
is 'open'.  This is a complex many-body problem in non-equilibrium statistical
mechanics.  In principle, the atoms in the protein channel, mobile ions, water
solvent, and lipid bilayer membrane are all dynamical variables, and the time
scale is long on the scale of all-atom MD simulations (many microseconds to
collect full statistics of the permeation process).  Fortunately, the ions
tend to move slowly compared to fluctuations of the surrounding protein, water
and membrane atoms, so a Langevin description of the ionic motion is often
appropriate.  Furthermore, prescriptions exist for computing the inputs into
such a simulation, e.g., the effective potential felt by the mobile ions, ionic
diffusion constants, etc.  We will present calculations of this type performed
on a recently crystallized bacterial pentameric ligand-gated ion channel, whose
eukaryotic counterparts play an important role in neuronal function.