Towards a reliable model of ion channels: three-dimensional simulation of ionic solutions (original) (raw)
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Simulation of biological ion channels with technology computer-aided design
Computer Methods and Programs in Biomedicine, 2007
Computer simulations of realistic ion channel structures have always been challenging and a subject of rigorous study. Simulations based on continuum electrostatics have proven to be computationally cheap and reasonably accurate in predicting a channel's behavior. In this paper we discuss the use of a device simulator, SILVACO, to build a solid-state model for KcsA channel and study its steady-state response. SILVACO is a well-established program, typically used by electrical engineers to simulate the process flow and electrical characteristics of solid-state devices. By employing this simulation program, we have presented an alternative computing platform for performing ion channel simulations, besides the known methods of writing codes in programming languages. With the ease of varying the different parameters in the channel's vestibule and the ability of incorporating surface charges, we have shown the wide-ranging possibilities of using a device simulator for ion channel simulations. Our simulated results closely agree with the experimental data, validating our model.
Ion-Channel Biosensors : Construction and Dynamic Modeling
2009
This paper deals with the construction and dynamic modeling of a novel biosensor that exploits the selective conductivity of biological ion channels. The biosensor comprises gramicidin A channels embedded in a synthetic tethered lipid bilayer. It provides highly sensitive and rapid detection of a wide variety of analytes. In this paper we outline the principle of operation of this ion channel biosensor including the fabrication of biochip arrays and reproducibility/stability issues. Then the electrical dynamics and chemical dynamics of the biosensor are modeled. The electrical dynamics are modeled by a second order linear system. The chemical dynamics of the biosensor response to analyte concentration in the reaction-rate-limited regime are modeled by a twotime scale nonlinear system of differential equations. Also the analyte concentration in the mass-transport-influenced regime is modeled by a partial differential equation subject to a mix of Neumann and Dirichlet boundary conditi...
Simulation of Biological Ionic Channels by Technology Computer-Aided Design
VLSI Design, 2001
This paper discusses the use of established Technology Computer-Aided Design (TCAD) tools and methodologies for the study of charge transport in molecular biology systems, like ionic channels, that display a behavior analogous to electronic devices. Continuum drift-diffusion and Monte Carlo methods can be applied to analyze steady-state and transient behavior of ionic channels over time scales that cannot be resolved practically by detailed molecular dynamics or quantum approaches. The difficult ion-water interaction can be lumped phenomenologically into mobility or scattering rate parameters, while the solution of Poisson equation over the complete domain provides a simple way to include external boundary conditions and image force effects at dielectric discontinuities. We present here some recent results of 3-D simulations for a gramicidin ion channel, obtained using the rapid prototyping computational platform PROPHET.
Bio-, Micro-, and Nanosystems (IEEE Cat. No.03EX733), 2003
Ion channels are proteins with a hole down their middle that control an enormous range of biological function. Channels are devices in the engineering sense of the word and engineering analysis helps understand their function. In particular, the current through channels is driven by the power supply of concentration gradient and electrical potential maintained by across membranes by cell metabolism. The current is controlled by the physics of ion permeation in a narrow charged tube. The wall of the tube contains a few fixed charges; the tube is less than 1 nm in diameter. The density of charge (mobile or fixed) in the tube is enormous, ∼10 molar. (Liquid water is ∼55 molar.) Movement of ions through this tube can be well described as the movement of charged spheres according to the Poisson-Drift-Diffusion equations of computational electronics. Selfconsistent computation of the electric field is a necessity. The chemical specificity of channels seems to arise from the crowding of charge in their narrow tunnel. A purely physical description of the energetics of crowded spheres is enough to explain the complex patterns of selectivity found in several types of channels.
Voltage sensing in ion channels: Mesoscale simulations of biological devices
Physical Review E, 2012
Electrical signaling via voltage-gated ion channels depends upon the function of a voltage sensor (VS), identified with the S1-S4 domain in voltage-gated K + channels. Here we investigate some energetic aspects of the sliding-helix model of the VS using simulations based on VS charges, linear dielectrics and whole-body motion. Model electrostatics in voltage-clamped boundary conditions are solved using a boundary element method. The statistical mechanical consequences of the electrostatic configurational energy are computed to gain insight into the sliding-helix mechanism and to predict experimentally measured ensemble properties such as gating charge displaced by an applied voltage. Those consequences and ensemble properties are investigated for two alternate S4 configurations, α-and 310-helical. Both forms of VS are found to have an inherent electrostatic stability. Maximal charge displacement is limited by geometry, specifically the range of movement where S4 charges and countercharges overlap in the region of weak dielectric. Charge displacement responds more steeply to voltage in the α-helical than in the 310-helical sensor. This difference is due to differences on the order of 0.1 eV in the landscapes of electrostatic energy. As a step toward integrating these VS models into a full-channel model, we include a hypothetical external load in the Hamiltonian of the system and analyze the energetic input-output relation of the VS.
Modeling ion channels: Past, present, and future
Ion channels are membrane-bound enzymes whose catalytic sites are ion-conducting pores that open and close (gate) in response to specific environmental stimuli. Ion channels are important contributors to cell signaling and homeostasis. Our current understanding of gating is the product of 60 plus years of voltage-clamp recording augmented by intervention in the form of environmental, chemical, and mutational perturbations. The need for good phenomenological models of gating has evolved in parallel with the sophistication of experimental technique. The goal of modeling is to develop realistic schemes that not only describe data, but also accurately reflect mechanisms of action. This review covers three areas that have contributed to the understanding of ion channels: traditional Eyring kinetic theory, molecular dynamics analysis, and statistical thermodynamics. Although the primary emphasis is on voltage-dependent channels, the methods discussed here are easily generalized to other stimuli and could be applied to any ion channel and indeed any macromolecule.
Ion Channels: History, Diversity, and Impact
Cold Spring Harbor protocols, 2017
From patch-clamp techniques to recombinant DNA technologies, three-dimensional protein modeling, and optogenetics, diverse and sophisticated methods have been used to study ion channels and how they determine the electrical properties of cells.