{"title":"The Joy of Markov Models—Channel Gating and Transport Cycling Made Easy","authors":"G. Zifarelli, P. Zuccolini, S. Bertelli, M. Pusch","doi":"10.35459/TBP.2019.000125","DOIUrl":null,"url":null,"abstract":"\n The behavior of ion channels and transporters is often modeled using discrete state continuous-time Markov models. Such models are helpful for the interpretation of experimental data and can guide the design of experiments by testing specific predictions. Here, we describe a computational tool that allows us to create Markov models of chosen complexity and to calculate the predictions on a macroscopic scale, as well on a single-molecule scale. The program calculates steady-state properties (current, state probabilities, and cycle frequencies), deterministic macroscopic and stochastic time courses, gating currents, dwell-time histograms, and power spectra of channels and transporters. In addition, a visual simulation mode allows us to follow the time-dependent stochastic behavior of a single channel or transporter. After a basic introduction into the concept of Markov models, real-life examples are discussed, including a model of a simple K+ channel, a voltage-gated sodium channel, a 3-state ligand-gated channel, and an electrogenic uniporter. In this manner, the article has a modular architecture, progressing from basic to more advanced topics. This illustrates how the MarkovEditor program can serve students to explore Markov models at a basic level but is also suited for research scientists to test and develop models on the mechanisms of protein function.","PeriodicalId":72403,"journal":{"name":"Biophysicist (Rockville, Md.)","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2021-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biophysicist (Rockville, Md.)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.35459/TBP.2019.000125","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 3
Abstract
The behavior of ion channels and transporters is often modeled using discrete state continuous-time Markov models. Such models are helpful for the interpretation of experimental data and can guide the design of experiments by testing specific predictions. Here, we describe a computational tool that allows us to create Markov models of chosen complexity and to calculate the predictions on a macroscopic scale, as well on a single-molecule scale. The program calculates steady-state properties (current, state probabilities, and cycle frequencies), deterministic macroscopic and stochastic time courses, gating currents, dwell-time histograms, and power spectra of channels and transporters. In addition, a visual simulation mode allows us to follow the time-dependent stochastic behavior of a single channel or transporter. After a basic introduction into the concept of Markov models, real-life examples are discussed, including a model of a simple K+ channel, a voltage-gated sodium channel, a 3-state ligand-gated channel, and an electrogenic uniporter. In this manner, the article has a modular architecture, progressing from basic to more advanced topics. This illustrates how the MarkovEditor program can serve students to explore Markov models at a basic level but is also suited for research scientists to test and develop models on the mechanisms of protein function.