Biomedical subjects

Dezso Boda

Publications and source records attributed to Dezso Boda.

3 recordsLinked to original sources

PubMed2006

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

Calcium-selective ion channels are known to have carboxylate-rich selectivity filters, a common motif that is primarily responsible for their high Ca(2+) affinity. Different Ca(2+) 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 electolyte 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, Ca(2+) is absorbed into the filter with higher probability than Na(+) because Ca(2+) 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, Ca(2+) 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 Ca(2+) affinity of the common four-carboxylate motif.

Calcium↗

PubMed2005

Relative permittivity of polar liquids. Comparison of theory, experiment, and simulation.

A molecular-based second-order perturbation theory is applied to calculate the relative permittivity of polar liquids. Our basic model is the dipolar hard sphere fluid. The main purpose of this work is to propose various approaches to take into account the molecular polarizability. In the continuum approach, we apply the Kirkwood-Fröhlich equation and use the high-frequency relative permittivity. The Kirkwood g-factor representing molecular correlations is calculated by a perturbation theory. In the molecular approach, the molecular polarizability is built into the model on the molecular level (the polarizable dipolar hard sphere fluid). To calculate the relative permittivity of this system, an equation obtained from a renormalization procedure is used. In both approaches, we apply a series expansion for the relative permittivity and show that these series expansions give results in better agreement with simulation data than the original equations. After testing our theoretical equations against our own Monte Carlo simulation results, we compare the results obtained from our theoretical equations and simulations to experimental data for amines, ethers, and halogenated, sulfur, and hydroxy compounds. We propose a procedure to calculate potential parameters (hard sphere diameter, reduced polarizability, and reduced dipole moment) from experimental data such as the permanent dipole moment, refractive index, density, and temperature. We show that for compounds of low relative permittivity the polarizable dipolar hard sphere (PDHS) model and the continuum approach give reasonable results. For nonassociative liquids of higher relative permittivity, the PDHS model overestimates experimental data due to unsatisfactory representation of the shape of the molecules. In the case of associative liquids, the PDHS model works well, and in some cases it underestimates the experimental values due to the unsatisfactory treatment of electrostatic interactions.

Journal Article↗

PubMed2001

Density Functional Study of a Simple Membrane Using the Solvent Primitive Model.

The model membrane, whose surfaces are maintained at the differing surface potentials, V(1) and V(2), on its inner and outer surfaces, that has been studied previously is extended to include explicit solvent molecules. The solvent primitive model, where the solvent molecules are treated as hard spheres, is used. In this study, the electrolyte can interact with the membrane both electrostatically and by means of a short-range van der Waals-like potential that can be attractive or repulsive. The bulk fluid beyond the outer surface is a four-component electrolyte consisting of the hard sphere solvent, two species of cations, and one species of anions. The membrane is impermeable to one of the cation species so that the fluid in the membrane and beyond the inner surface is a three-component electrolyte. Previously, we studied this model membrane by computer simulation and density functional theory (DFT) and found this theory to be quite accurate. Here we report further results, obtained using DFT, from which results can be obtained much more easily than from simulations. The density profiles of the electrolyte near the membrane and the charge-potential relationship of the membrane surfaces under a wider variety of conditions than is possible by simulation are studied. The presence of the solvent molecules leads to a greater excluded volume. As a result, the density profiles are oscillatory, whereas they are monotonic when a molecular model for the solvent is not used. The potential versus charge relationship is strongly influenced by the solvent density. In addition to the electrostatic interactions, the effect of a van der Waals interaction on the solvent molecules is considered. Copyright 2001 Academic Press.

Journal Article↗