Membrane Proteins

Membrane Proteins

Membrane Proteins

Membrane protein folding does not necessarily follow the same empirical principles which describe soluble globular protein folding and dynamics. We are interested in extending the methods we've developed to membrane proteins.

For many potassium channels, tetramerization domains in either the N- or C-terminal of the pore domain assist in tetramer assembly by increasing local concentrations of monomeric subunits. The question we would like to understand is - to what extent do the pore domain monomers adopt a native-like structure found in tetramers?

Approach

  • We use a combination of molecular dynamics (MD) simulations, Markov State Modelling (MSM), and experimental biophysical techniques to address the aforementioned question.
  • Through MD simulations and MSM analysis, we found that the potassium channel monomers do not adopt a native-like structure but rather a non-native structure stabilized by intra-monomer salt-bridges that mimic inter-monomer salt-bridges.