Ionic Coulomb blockade oscillations and the physical origins of permeation, selectivity, and their mutation transformations in biological ion channels

Lead Research Organisation: University of Warwick
Department Name: Sch of Engineering

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Publications

10 25 50

publication icon
Guardiani C (2017) Sodium Binding Sites and Permeation Mechanism in the NaChBac Channel: A Molecular Dynamics Study. in Journal of chemical theory and computation

publication icon
Barabash M (2021) Origin and control of ionic hydration patterns in nanopores in Communications Materials

publication icon
Barabash ML (2021) Field-Dependent Dehydration and Optimal Ionic Escape Paths for C2N Membranes. in The journal of physical chemistry. B

publication icon
Guardiani C (2019) Different roles for aspartates and glutamates for cation permeation in bacterial sodium channels. in Biochimica et biophysica acta. Biomembranes

publication icon
Guardiani C (2022) Computational methods and theory for ion channel research in Advances in Physics: X

 
Description The project led to an understanding of the key physical mechanisms underlying conductivity in biological ion channels. The ion channels are essential to biological cell functioning, and their dysfunction leads to a wide range of diseases.
In the project, we applied a combination of physiological experiments that studied the conduction of sodium ion channels and their mutants, simulations of molecular level channel models using high-performance computing and physics-based theory for developing a simplified description. The combination led to a comprehensive picture of channel conductivities and confirmed an initial project idea that electrostatic effects in narrow-charged channels play a leading role. We have developed a theoretical and computational framework for predicting the influence of the charge distribution in the channel and confirmed the prediction in molecular simulations and experimentally. The developed framework substantially impacts the fundamental science of biological channels and provides a pathway for pharmaceutical controlling of biological channels. Also, we have demonstrated that the framework is applicable to artificial nanochannels such as carbon nanotubes. After the award was finished, we started to expand the framework for developing functional solid-state nanodevices for a diverse range of applications, including water desalination and DNA sequencing.
During the project, we developed a novel model of the NaChBac bacterial channel and novel computational approaches for analysing the molecular-level channel models. These outcomes were described in a series of publications. Therefore, they are available to the scientific community.
Exploitation Route The main project findings were published and have been presented at several conferences. The developed models and computational approaches are available for the scientific community to use further.
We extended the project outcome, and in a series of publications (after the award finished), we demonstrated how the developed theoretical and computational framework can be applied to artificial solid-state nanochannels for controlling water and ion transport through them. The project outcomes provide a way forward for bridging biological and artificial channels and the development of biomimetic and bioinspired engineered channels. This way could lead to novel design principles for developing new chemical materials.
Sectors Chemicals

Digital/Communication/Information Technologies (including Software)

Education

Pharmaceuticals and Medical Biotechnology

Other

 
Description Proposal for a Tier 2 Centre - HPC Midlands Plus
Amount £3,200,000 (GBP)
Funding ID EP/P020232/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 12/2016 
End 06/2021
 
Title New computational structure of NaChBac ion channel 
Description A pore subdomain of NaChBac ion channel from Bacillus halodurans has been developed via homology modelling 
Type Of Material Computer model/algorithm 
Year Produced 2017 
Provided To Others? Yes  
Impact Reseach community has been provided by a computational model which can be used for establishing links and understanding with a large volume of experimental data related to the NaChBac channel. 
URL http://wrap.warwick.ac.uk/84894
 
Description HPC Midland Plus Athena 
Organisation HPC Midlands Plus
Sector Public 
PI Contribution Our research team has developed simulation framework for modelling ion channels and analyzing the outcome
Collaborator Contribution The partner is providing infrastructure, resources and technical support for simulations
Impact 2 papers has resulted from this collaboration
Start Year 2017
 
Description Lancaster Theory and Experiment 
Organisation Lancaster University
Department Department of Physics
Country United Kingdom 
Sector Academic/University 
PI Contribution Warwick University contributed molecular dynamics simulations of the ion channels. Warwick and Lancaster each contributed expertise in stochastic nonlinear dynamics and analysis of experimental data.
Collaborator Contribution Lancaster University mostly contributed expertise in the analytic theory of biological ion channels, coupled with Brownian dynamics simulations of the permeation process and conduct experimental investigation of permeation and selectivity in ion channels and their mutants. Lancaster and Warwick each contributed expertise in stochastic nonlinear dynamics.
Impact Some 10 Lancaster/Warwick joint scientific papers have been published. the main impact of the joint work has been in scientific progress.
Start Year 2015
 
Description Lancaster Theory and Experiment 
Organisation Lancaster University
Department Division of Biomedical and Life Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Warwick University contributed molecular dynamics simulations of the ion channels. Warwick and Lancaster each contributed expertise in stochastic nonlinear dynamics and analysis of experimental data.
Collaborator Contribution Lancaster University mostly contributed expertise in the analytic theory of biological ion channels, coupled with Brownian dynamics simulations of the permeation process and conduct experimental investigation of permeation and selectivity in ion channels and their mutants. Lancaster and Warwick each contributed expertise in stochastic nonlinear dynamics.
Impact Some 10 Lancaster/Warwick joint scientific papers have been published. the main impact of the joint work has been in scientific progress.
Start Year 2015