Transcending Markov: non-Markovian rate processes of thermosensitive TRP ion channels
The Markov state model (MSM) is a popular theoretical tool for describing the hierarchy of time scales involved in the function of many proteins especially ion channel gating. An MSM is a particular case of the general non-Markovian model, where the rate of transition from one state to another does...
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| Format: | Article |
| Language: | English |
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The Royal Society
2023-08-01
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| Series: | Royal Society Open Science |
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| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsos.230984 |
| _version_ | 1797738910092099584 |
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| author | Yuval Ben-Abu Stephen J Tucker Sonia Contera |
| author_facet | Yuval Ben-Abu Stephen J Tucker Sonia Contera |
| author_sort | Yuval Ben-Abu |
| collection | DOAJ |
| description | The Markov state model (MSM) is a popular theoretical tool for describing the hierarchy of time scales involved in the function of many proteins especially ion channel gating. An MSM is a particular case of the general non-Markovian model, where the rate of transition from one state to another does not depend on the history of state occupancy within the system, i.e. it only includes reversible, non-dissipative processes. However, an MSM requires knowledge of the precise conformational state of the protein and is not predictive when those details are not known. In the case of ion channels, this simple description fails in real (non-equilibrium) situations, for example when local temperature changes, or when energy losses occur during channel gating. Here, we show it is possible to use non-Markovian equations (i.e. offer a general description that includes the MSM as a particular case) to develop a relatively simple analytical model that describes the non-equilibrium behaviour of the temperature-sensitive transient receptor potential (TRP) ion channels, TRPV1 and TRPM8. This model accurately predicts asymmetrical opening and closing rates, infinite processes and the creation of new states, as well as the effect of temperature changes throughout the process. This approach therefore overcomes the limitations of the MSM and allows us to go beyond a mere phenomenological description of the dynamics of ion channel gating towards a better understanding of the physics underlying these processes. |
| first_indexed | 2024-03-12T13:49:41Z |
| format | Article |
| id | doaj.art-16a19a3f7a2e4fbfa34ebe29fc413af4 |
| institution | Directory Open Access Journal |
| issn | 2054-5703 |
| language | English |
| last_indexed | 2024-03-12T13:49:41Z |
| publishDate | 2023-08-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Royal Society Open Science |
| spelling | doaj.art-16a19a3f7a2e4fbfa34ebe29fc413af42023-08-23T07:05:17ZengThe Royal SocietyRoyal Society Open Science2054-57032023-08-0110810.1098/rsos.230984Transcending Markov: non-Markovian rate processes of thermosensitive TRP ion channelsYuval Ben-Abu0Stephen J Tucker1Sonia Contera2Physics Unit, Sapir Academic College, Sderot, Hof Ashkelon 79165, IsraelClarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UKClarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UKThe Markov state model (MSM) is a popular theoretical tool for describing the hierarchy of time scales involved in the function of many proteins especially ion channel gating. An MSM is a particular case of the general non-Markovian model, where the rate of transition from one state to another does not depend on the history of state occupancy within the system, i.e. it only includes reversible, non-dissipative processes. However, an MSM requires knowledge of the precise conformational state of the protein and is not predictive when those details are not known. In the case of ion channels, this simple description fails in real (non-equilibrium) situations, for example when local temperature changes, or when energy losses occur during channel gating. Here, we show it is possible to use non-Markovian equations (i.e. offer a general description that includes the MSM as a particular case) to develop a relatively simple analytical model that describes the non-equilibrium behaviour of the temperature-sensitive transient receptor potential (TRP) ion channels, TRPV1 and TRPM8. This model accurately predicts asymmetrical opening and closing rates, infinite processes and the creation of new states, as well as the effect of temperature changes throughout the process. This approach therefore overcomes the limitations of the MSM and allows us to go beyond a mere phenomenological description of the dynamics of ion channel gating towards a better understanding of the physics underlying these processes.https://royalsocietypublishing.org/doi/10.1098/rsos.230984ion channelnon-Markovian random processrandom processTauberian theoremsnon-equilibrium physicsstatistical physics |
| spellingShingle | Yuval Ben-Abu Stephen J Tucker Sonia Contera Transcending Markov: non-Markovian rate processes of thermosensitive TRP ion channels Royal Society Open Science ion channel non-Markovian random process random process Tauberian theorems non-equilibrium physics statistical physics |
| title | Transcending Markov: non-Markovian rate processes of thermosensitive TRP ion channels |
| title_full | Transcending Markov: non-Markovian rate processes of thermosensitive TRP ion channels |
| title_fullStr | Transcending Markov: non-Markovian rate processes of thermosensitive TRP ion channels |
| title_full_unstemmed | Transcending Markov: non-Markovian rate processes of thermosensitive TRP ion channels |
| title_short | Transcending Markov: non-Markovian rate processes of thermosensitive TRP ion channels |
| title_sort | transcending markov non markovian rate processes of thermosensitive trp ion channels |
| topic | ion channel non-Markovian random process random process Tauberian theorems non-equilibrium physics statistical physics |
| url | https://royalsocietypublishing.org/doi/10.1098/rsos.230984 |
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