Ion channels are membrane-bound enzymes that utilize ion flux to perform a variety of biological functions, such as intercellular communication and signaling, osmotic stress responses, muscle contraction, etc. Since ion channels are important contributors to cell signaling and homeostasis, ion channels are important targets for new drug development. With the support of our advanced protein engineering platform established for many years, Creative BioMart has successfully established a modeling and simulation platform for ion channels. Our scientists provide you with a comprehensive customized ion channel modeling service to identify a given ion channel and develop a computational model of the ion channel, which has important implications for future drug development efforts.

Ion channels are pore-forming membrane proteins that allow ions to pass through channel pores, and their catalytic sites are ion-conducting pores that open and close in response to specific environmental stimuli (voltage, ligand concentration, membrane tension, temperature, etc.). Since the discovery of excitable ionic membranes, modeling and simulations have been integral to the development of the field. Hundreds of different types of ion channels have been discovered. However, modeling and simulations of ion channels are often limited by the experimental knowledge about them. A key challenge in this field remains to predict the electrical response of membranes containing ion channels to external stimuli such as transmembrane voltages, chemical ligands, and tension. Most researchers working in the field of computer modeling of ion channels employ the "no structure-no study" rule to predict the structural architecture of a channel from its sequence or ion conductance properties.

Fig 1. A schematic illustrations of the PNP (a) BD (b) and all-atom MD (c) modeling methods applied to the same system. (Maffeo C, et al., 2012)

Services

Advances in computational techniques and methods for determining the structure of membrane proteins have made modeling and simulation of ion channels an integral part of future drug development efforts. Creative BioMart is committed to the development of computational models of ion channels, providing ion channel models with good signal readout and stability, including gramicidin A channels, outer membrane porin (OMP) channels, mechanosensitive channels, potassium channels, calcium channels, nicotinic acetylcholine receptors body (nAChR) channels and voltage-dependent anion channels (VDAC), etc.

Ion channels are complex systems with many degrees of freedom, making it difficult to model atomic details. We employ the following computational methods to study the ion channel model:

• All-atom molecular dynamics (MD): by explicitly describing all atoms and most interatomic interactions of a system of interest, it can provide unparalleled insight into the physical mechanisms underlying the biological function of biological macromolecules.
• Brownian dynamics (BD): allowing the simulation of explicit ion permeation on microsecond to millisecond timescales by implicitly manipulating solvent molecules.
• Poisson-Nernst-Planck (PNP): this method is very effective in predicting the effect of channel geometry on current-voltage dependence at physiological voltages and can be used to screen for mutations affecting channel conductance.

Note that each method has limitations and advantages. The MD method is considered to be the most computationally expensive but also the most accurate method. PNP and BD methods are generally less computationally expensive, but also provide less detail. At the same time, the spatiotemporal scope of the MD method is the smallest. Considering the characteristics of these ion channel modeling methods, we will develop the best solution for you, from ion channel screening, active compound verification and specificity analysis to ion channel modeling and simulation.

Service Principle

Creative BioMart is based on innovative, pragmatic and honest, adhering to the tenet of "Quality is our life, providing customers with the best quality service", providing customized services to customers around the world.

We will be glad to discuss details of intended interaction studies with you and develop experimental strategies/methods tailored to your requirement. Our customer service representatives are enthusiastic and trustworthy 24 hours a day, Monday to Friday. If you are interested in our services, please do not hesitate to contact us for more information or to discuss in detail.

References

1. Maffeo C, Bhattacharya S, et al.. (2012) Modeling and simulation of ion channels. Chem Rev. 112 (12): 6250-6284.
2. Levitt D G. (1999) Modeling of ion channels[J]. The Journal of general physiology. 113 (6): 789-794.

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