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.
People |
ORCID iD |
| Igor Khovanov (Principal Investigator) | |
| P Rodger (Co-Investigator) |
Publications
Guardiani C
(2022)
Computational methods and theory for ion channel research
in Advances in Physics: X
Guardiani C
(2019)
Different roles for aspartates and glutamates for cation permeation in bacterial sodium channels.
in Biochimica et biophysica acta. Biomembranes
Barabash M
(2021)
Origin and control of ionic hydration patterns in nanopores
in Communications Materials
Gibby W
(2021)
Application of a Statistical and Linear Response Theory to Multi-Ion Na+ Conduction in NaChBac
in Entropy
Fedorenko OA
(2020)
Changes in Ion Selectivity Following the Asymmetrical Addition of Charge to the Selectivity Filter of Bacterial Sodium Channels.
in Entropy (Basel, Switzerland)
Barabash M
(2019)
From the Potential of the Mean Force to a Quasiparticle's Effective Potential in Narrow Ion Channels
in Fluctuation and Noise Letters
Guardiani C
(2017)
Sodium Binding Sites and Permeation Mechanism in the NaChBac Channel: A Molecular Dynamics Study.
in Journal of chemical theory and computation
Guardiani C
(2017)
On the selectivity of the NaChBac channel: an integrated computational and experimental analysis of sodium and calcium permeation.
in Physical chemistry chemical physics : PCCP
Soskin S
(2019)
Mechanism of resonant enhancement of electron drift in nanometer semiconductor superlattices subjected to electric and inclined magnetic fields
in Physical Review B
| 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 |