[nano501] Nano 501 Tutorial, Wednesday, March 26

[Goodman, Alicia D.]

Ionic Selectivity in Channels: complex biology created by the balance of 
simple physics

Dr. Bob Eisenberg, Rush Medical University

March 26, 2008, 12:30 pm FU Room, POTR 234

An important class of biological molecules—proteins called ionic 
channels—conduct ions (like Na+ , K+ , Ca2+ , and Cl- ) through a narrow 
tunnel of fixed charge (‘doping’). Ionic channels control the movement 
of electric charge and current across biological membranes and so play a 
role in biology as significant as the role of transistors in computers: 
a substantial fraction of all drugs used by physicians act on channels. 
Channels can be studied in the tradition of physical science because the 
ions near and in channels form an ionic liquid, a plasma in both the 
biological and physical meaning of the word. Poisson-Drift diffusion 
equations familiar in physics (called the PNP or Poisson Nernst Planck 
equations in biophysics) form can be extended to describe ‘chemical’ 
phenomena like selectivity with some success by including correlations 
produced by the finite size of the ions. Complex phenomena of 
selectivity in this reduced model comes from the balance of simple 
attractive (mostly electrostatic) and repulsive (mostly excluded volume) 
forces. Preformed structures and chemical bonds like cation-? 
interactions play no role in these models. Two parameters (volume and 
dielectric coefficient) set to invariant values are enough to predict 
the selectivity of DEEA calcium channels in a wide range of solutions. 
The same model and parameters predict the very different properties of 
the DEKA sodium channel, including selectivity for Na+ vs. K+ in a wide 
variety of solutions. The same reduced model accounts for the properties 
of the RyR channel in some 100 solutions, and predicted several complex 
experimental results before they were observed. Nonselective bacterial 
channels have been mutated into selective calcium channels as predicted 
by the model and selective nanoholes in plastic have been made. In these 
models, the structure of ‘side chains’ is an output of the model, in 
marked contrast to the usual view of crystallographic structures. We are 
unaware of other models — crystallographic or computational — that deal 
successfully with selectivity phenomena over a range of concentrations, 
mutations and channel types.

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Alicia Goodman
Administrative Assistant
Network for Computational Nanotechnology
Purdue University
Birck Nanotechnology Center
1205 West State Street
West Lafayette, IN  47907
Phone:  765-494-7715
Fax:  765-494-0811
email:  goodman at purdue.edu
website:  www.nanoHUB.org