Bayesian approaches for mechanistic ion channel modeling

Methods Mol Biol. 2013:1021:247-72. doi: 10.1007/978-1-62703-450-0_13.

Abstract

We consider the Bayesian analysis of mechanistic models describing the dynamic behavior of ligand-gated ion channels. The opening of the transmembrane pore in an ion channel is brought about by conformational changes in the protein, which results in a flow of ions through the pore. Remarkably, given the diameter of the pore, the flow of ions from a small number of channels or indeed from a single ion channel molecule can be recorded experimentally. This produces a large time-series of high-resolution experimental data, which can be used to investigate the gating process of these channels. We give a brief overview of the achievements and limitations of alternative maximum-likelihood approaches to this type of modeling, before investigating the statistical issues associated with analyzing stochastic model reaction mechanisms from a Bayesian perspective. Finally, we compare a number of Markov chain Monte Carlo algorithms that may be used to tackle this challenging inference problem.

MeSH terms

  • Algorithms*
  • Bayes Theorem
  • Computer Simulation
  • Humans
  • Ion Channel Gating*
  • Ion Channels / chemistry
  • Ion Channels / metabolism*
  • Markov Chains
  • Models, Biological*
  • Monte Carlo Method
  • Systems Biology

Substances

  • Ion Channels