Modeling of Interactions & Dynamics in Membrane Helices and Voltage-Gated Ion Channels


Project leader


Funding source

Swedish Research Council - Vetenskapsrådet (VR)


Project Details

Start date: 01/01/2008
End date: 31/12/2010
Funding: 2100000 SEK


Description

The goal of our research is to understand membrane proteins, in particular ion channels, and e.g. activation by applied voltage. Our tools range from bioinformatics and molecular modeling through simplified models, simulation, and free energy calculations in our Gromacs toolkit. Specifically, we will focus on: MEMBRANE-HELIX INSERTION We have derived free energies of amino acids in membranes, and will calculate how insertion is affected by translocon and protein-lipid interactions, for instance to explain how ion channel function depends on lipid charge. SIMULATIONS OF VOLTAGE-GATED ION CHANNELS One of the highest charged of all membrane helices is S4 in VGIC’s, which moves in a voltage. We will simulate how S4 is stabilized, and not only that – with elevated temperatures and a new efficiently scaling version of Gromacs we will pursue an landmark parallel simulation of the entire gating motion over 5 microsec. VOLTAGE-SENSOR-ONLY DOMAINS have recently been discovered in membranes, and we will model these to explain the observed proton current, examine structural transition and dynamics, and explain sequence-function patterns. MODELING & DESIGN OF HELIX DIMERIZATION Membrane helix dimers are important for signaling and as anchors, but some mutations are known to cause tumor growth. We will develop better dimer models, predict dimerization free energies, and finally attempt to design “intercepting peptides”, with fascinating possible applications in cancer treatment.

Last updated on 2017-31-03 at 12:59