Single-channel Markov modelling of voltage-gated ion channels with simulations and implementation of the 2D-Fit algorithm on High Performance Computing Cluster

• Applicant: Privatdozent Dr. Tobias Huth
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Biophysics ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 422920516

In this project, we want to explore the computational power of HPC-Cluster for modelling single-channel patch-clamp data with Markov models. The 2D-Dwell-Time fit with simulations of time series captures gating kinetics with a high background of noise and can extract rate constants beyond the recording bandwidth. That makes the 2D-Fit exceptional valuable for relating ion-channel kinetics with data from simulations of single molecules. In addition, 2D-distributions preserve the coherency of connected states. Thereby the algorithm can extract the full complexity of underlying models and distinguish different models. With the computing power of HPC-Cluster at hand we will be able to rigorous test the algorithm and optimize the settings for analysing single-channel time series. Thereafter we want to implement new features to increase the power and the versatility of the algorithm. The second important aim of the project is to acquire and model experimental single-channel patch-clamp data. We want to understand the interaction of β-secretase BACE1 with ion channels of the KCNQ family and the mechanisms how the protease alters gating in the framework of Alzheimer’s disease (AD).The 2D-Fit program will be made freely available for download under the GNU General Public License (GNU GPLv3). It will facilitate research dedicated to understanding the function of ion channels by extracting complete and robust gating models in short time. Finally, we want to probe the usefulness of the 2D-Fit to analyse other data from single ion channels and data related to optical single-molecule methods.

• DFG Programme: Research Grants
• Major Instrumentation: Single-channel patch-clamp setup
• Instrumentation Group: 5040 Spezielle Mikroskope (außer 500-503)