Analytical models of calcium binding in a calcium channel

• Published in: The Journal of chemical physics Vol. 141; no. 7; p. 075102
• Main Authors: Liu, Jinn-Liang, Eisenberg, Bob
• Format: Journal Article
• Language: English
• Published: United States 21.08.2014
• Subjects: Binding Sites; Calcium - metabolism; Calcium Channels - chemistry; Calcium Channels - metabolism; Models, Molecular; Poisson Distribution; Protein Binding; Protein Conformation
• ISSN: 1089-7690
• DOI: 10.1063/1.4892839

The anomalous mole fraction effect of L-type calcium channels is analyzed using a Fermi like distribution with the experimental data of Almers and McCleskey [J. Physiol. 353, 585 (1984)] and the atomic resolution model of Lipkind and Fozzard [Biochemistry 40, 6786 (2001)] of the selectivity filter of the channel. Much of the analysis is algebraic, independent of differential equations. The Fermi distribution is derived from the configuration entropy of ions and water molecules with different sizes, different valences, and interstitial voids between particles. It allows us to calculate potentials and distances (between the binding ion and the oxygen ions of the glutamate side chains) directly from the experimental data using algebraic formulas. The spatial resolution of these results is comparable with those of molecular models, but of course the accuracy is no better than that implied by the experimental data. The glutamate side chains in our model are flexible enough to accommodate different types of binding ions in different bath conditions. The binding curves of Na(+) and Ca(2+) for [CaCl2] ranging from 10(-8) to 10(-2) M with a fixed 32 mM background [NaCl] are shown to agree with published Monte Carlo simulations. The Poisson-Fermi differential equation-that includes both steric and correlation effects-is then used to obtain the spatial profiles of energy, concentration, and dielectric coefficient from the solvent region to the filter. The energy profiles of ions are shown to depend sensitively on the steric energy that is not taken into account in the classical rate theory. We improve the rate theory by introducing a steric energy that lumps the effects of excluded volumes of all ions and water molecules and empty spaces between particles created by Lennard-Jones type and electrostatic forces. We show that the energy landscape varies significantly with bath concentrations. The energy landscape is not constant.