Simulation of Ion Permeation and Selectivity

Creative Bioarray uses a variety of simulation methods to provide clients with simulation services of ion channel permeability and selectivity, especially Na_v channels, which is helpful to understand the principle of Na⁺ permeation and selectivity in a large class of voltage-gated ion channels. Our professional scientific services will help you obtain reliable experimental results and contribute to your drug design targeting ion channels.

Introduction

In excitable cells, there are two types of voltage-gated ion channels, including Na_v and K_v channels, which specialize in Na⁺ and K⁺ permeation, respectively. These channels are able to respond to the transmembrane voltage and change the conformational state to allow one or the other of these cations to flow according to its electrochemical gradient. In mammalian skeletal muscle, the asymmetry of intracellular and extracellular ion concentration is the key to the process of selective ion permeation. Elucidating the molecular basis of selective ion permeation is important for understanding the function of wild-type ion channels and pathogenic mutations.

At present, molecular dynamics simulation has been widely used to study the molecular basis of ion transport in the voltage-gated ion channel model. In recent years, the elucidation of the three-dimensional structure of bacterial Na_v channels has opened the way for the computational study of these membrane proteins, which helps to provide a unique perspective for molecular mechanisms of ionic permeation in weakly selective channels.

Fig. 1 Free simulation of permeation in a K⁺ channel. (Flood, 2019)

Our Services

Computer simulations of ion channels can be used to identify molecular driving forces for ion binding, permeation, and selectivity. Our research team is committed to establishing various simulation methods with different force field parameters, molecular models, sampling algorithms, sampling ranges, and simulation times to help clients select the best protocol to improve the accuracy of simulation results. Based on our simulation services, we provide our clients with the following services, including but not limited to:

Effective kinetic analysis of ion movements.
Calculation of ion channel potential of mean force (PMF).
Sampling of both ion and protein movements, as well as ample permeation events to statistically evaluate the current.
Free simulation of permeation in K⁺ channels.
Ionic selectivity simulation of Na_v channels.

Analysis of selectivity over K⁺ using biased sampling or unbiased sampling.
Analysis of selectivity over Ca²⁺ using unbiased and biased sampling.
Analysis of selectivity over Ca²⁺ using quantum calculations.

Successful Service Cases

We have successfully helped clients to complete the following projects:

Analysis of sodium-selective ion permeation in bacterial Na_v channels
Analysis of sodium-selective ion permeation in mammalian Na_v channels
Analysis of sodium-selective ion permeation in acid-sensing ion channels

Creative Bioarray is committed to providing clients with ion channel permeability and selectivity simulation services. Our researchers have made continuous efforts to propose strategies that can be used to address the differences between simulation studies to improve future computational studies of permeation and selectivity of ion channels. If you are interested in our services, please feel free to contact us for more details.

Reference

Flood, E.; et al. Atomistic simulations of membrane ion channel conduction, gating, and modulation. Chemical Reviews, 2019, 119(13): 7737-7832.

For Research Use Only.