What do we do?
At the Computational Biophysics Group, we are interested in the structure-function relationship of membrane proteins. Using molecular mechanics simulations and statistical approaches, our group aims at understanding the microscopic mechanisms underlying the functions of proteins involved in the membrane transport of various substrates, to discover how the functions of proteins emerge from their 3D structure. A central topic of study revolves around the elucidation of gating mechanisms which regulate ion permeation and the activity of potassium channels in excitable cells, and the resulting impact on neuron signalling. Other subjects of interest involve transport mechanisms that are ATP-dependent or proton-coupled, and the mechanisms of protein folding.
In the context of the Human Brain Project, one of the EU Flagship projects, we defined a new generation of kinetic models of K channels that will eventually be used in neuron models at the core of the brain simulator. These new kinetic models summarize all of our knowledge of K channels accumulated over decades through structural, functional, and simulation studies. This provides an ideal framework to better understand the role played by each of the channels in the modulation and propagation of action potentials within neurons. On this basis, we elaborated new hypotheses on the mechanisms that sustain working (or short) memory in the brain. We are currently developing neuron network models to test these hypotheses.
Main publications 2016
- Sauer MM et al. Catch-bond mechanism of the bacterial adhesin FimH. Nat. Commun. 2016; 7(7), 10738, DOI: 10.1038/ncomms10738.
- Leung HTA et al. A rigorous and efficient method to reweight very large conformational ensembles using average experimental data and to determine their relative information content. J. Chem Theory Comput. 2016; 12(1):383-94.