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 concerns the elucidation of gating mechanisms regulating 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.
Thanks to the latest generation of molecular mechanics force field, our team was able to elucidate molecular mechanisms on a scale that is barely accessible by experimental approaches. For example, based on crystallographic and functional data, the proteins of the Rh family were described as ammonia channels which allow NH3 to diffuse down its gradient. The group’s free energy simulations revealed that Rh proteins actually recruit NH4+, which can then diffuse as NH3 once a proton has been transferred to a conserved histidine. Recruitment of NH4+ is more efficient than that of NH3 by orders of magnitude because of its higher abundance and binding affinity, and thus explains better the measured transport rates. Their simulations revealed mechanisms which provide a new perspective on the structural data and allow for a more rigorous interpretation of the functional data.
Main publications 2015
- Baday S et al. Mechanism of NH4+ Recruitment and NH3 Transport in Rh Proteins. Structure 2015;23:1550-7.
- Bignucolo O et al. Backbone Hydration Determines the Folding Signature of Amino Acid Residues. J Am Chem Soc 2015;137(13):4300-3.
- Xu Y et al. Allocrite sensing and binding by the breast cancer resistance protein (ABCG2) and P-glycoprotein (ABCB1). Biochemistry 2015;54(40):6195-206.