The effect of protein dielectric coefficient on the ionic selectivity of a calcium channel

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Permanent URL	http://hdl.lib.byu.edu/1877/1384
Title	The effect of protein dielectric coefficient on the ionic selectivity of a calcium channel
BYU Creator	Henderson, Douglas
Creator	Boda, Dezso Valisko, Monika Eisenberg, Bob Nonner, Wolfgang Gillespie, Dirk
Keywords	protein dielectric coefficient; ionic selectivity; calcium; carboxylate-rich selective filters; Monte Carlo simulations
Description/Abstract	Calcium-selective ion channels are known to have carboxylate-rich selectivity filters, a common motif that is primarily responsible for their high Ca2+ affinity. Different Ca2+ affinities ranging from micromolar (the L-type Ca channel) to millimolar (the ryanodine receptor channel) are closely related to the different physiological functions of these channels. To understand the physical mechanism for this range of affinities given similar amino acids in their selectivity filters, we use grand canonical Monte Carlo simulations to assess the binding of monovalent and divalent ions in the selectivity filter of a model Ca channel. We use a reduced model where the electrolyte is modeled by hard-sphere ions embedded in a continuum dielectric solvent, while the interior of protein surrounding the channel is allowed to have a dielectric coefficient different from that of the electrolyte. The induced charges that appear on the protein/lumen interface are calculated by the induced charge computation method [Boda et al., Phys. Rev. E 69, 046702 (2004)]. It is shown that decreasing the dielectric coefficient of the protein attracts more cations into the pore because the protein's carboxyl groups induce negative charges on the dielectric boundary. As the density of the hard-sphere ions increases in the filter, Ca2+ is absorbed into the filter with higher probability than Na+ because Ca2+ provides twice the charge to neutralize the negative charge of the pore (both structural carboxylate oxygens and induced charges) than Na+ while occupying about the same space (the charge/space competition mechanism). As a result, Ca2+ affinity is improved an order of magnitude by decreasing the protein dielectric coefficient from 80 to 5. Our results indicate that adjusting the dielectric properties of the protein surrounding the permeation pathway is a possible way for evolution to regulate the Ca2+ affinity of the common four-carboxylate motif.
Source	Boda, Dezso, Monika Valisko, Bob Eisenberg, Wolfgang Nonner, Douglas Henderson, and Dirk Gillespie."The effect of protein dielectric coefficient on the ionic selectivity of a calcium channel." The Journal of Chemical Physics 125 (2006).;
Publisher	AIP
Date Original	2006-07-18
Language	English eng en
Publication Type	Articles
Type	Text
Format	application/pdf
Owning Institution	Brigham Young University
BYU College	College of Physical and Mathematical Sciences
BYU Department	Chemistry and Biochemistry
Copyright Status	(c) 2006 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in The Journal of Chemical Physics and may be found at http://link.aip.org/link/?JCPSA6/125/034901/1;
Copyright Use Information	http://www.lib.byu.edu/generic_copyright.html

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The effect of protein dielectric coefficient on the ionic selectivity of a calcium channel

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