Project description
A charge-scaled force field model of ion-related biological processes
Biological systems rely on the flow of electrical charge for myriad signalling functions, often carried out by ions rather than electrons. Modelling these processes is a prerequisite to understanding them and harnessing the insight in therapies for ion-related pathologies. However, current models lack a description of an important effect of ions on the environment, namely electronic polarisation, which results in inaccuracies. Funded by the European Research Council, the Q-SCALING project will address this deficiency using machine learning techniques. The aim is to build a de novo comprehensive force field for biological systems that accounts for electronic polarisation in a mean-field way via charge scaling. The newly developed charge-scaled force field model will enable accurately addressing ion-specific processes from molecular to organ levels.
Objective
Electrical stimuli are essential for a plethora of biological functions. Unlike in electronics, where electrons form currents, nature rather exploits ions as charge carriers. Lack of a consistent molecular picture of action of ions impairs progress in fundamental understanding of ion-controlled biological processes and in designing smart strategies for fixing ion-related pathological conditions. Molecular simulations represent a powerful tool for modelling such processes, however, they can only be as good as is the underlying interaction model (force field). A major drawback of commonly used force fields is the lack of description of electronic polarization, which results in severe artifacts such as a dramatic over-binding of ions, preventing, e.g. accurate modelling of calcium signalling processes. This now well-recognized deficiency hampers faithful modelling of complex ion-involving biological processes.
We will employ machine learning techniques to build a de novo comprehensive force field for biological systems, that accounts for electronic polarization in a mean field way via charge scaling. This approach will qualitatively improve modelling of ions in biological contexts without additional computational costs. This will allow us to address accurately the following highly relevant ion-specific processes of increasing complexity from molecular over cellular to organ levels:
1. Dissolution of radical anions of aromatic molecules as key intermediates in technologically and biologically important non-enzymatic and enzymatic Birch reduction processes.
2. Direct membrane translocation of cationic cell penetrating peptides with a potential of drug delivery.
3. Circulation of calcium ions as signalling charge carriers through ion channels of hair cells in the cochlea.
At the same time, the newly developed charge scaled force field will be made freely available to the community for further development and ready to be used within major simulation program packages.
Fields of science
- natural sciencesbiological sciencescell biologycell signaling
- natural sciencesbiological sciencesbiochemistrybiomolecules
- natural sciencescomputer and information sciencescomputational sciencemultiphysics
- natural sciencescomputer and information sciencesartificial intelligencemachine learning
- natural sciencescomputer and information sciencessoftwaresoftware applicationssimulation software
Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
16610 Praha 6
Czechia