Future research leaders: Molecular Modeling & Design of Membrane Protein Interactions


Project leader


Funding source

Swedish Foundation for Strategic Research - Stiftelsen för strategisk forskning


Project Details

Start date: 01/03/2008
End date: 01/03/2013
Funding: 8500000 SEK


Description

The goal of our research is to understand how membrane proteins fold, interact and function. Our tools range from bioinformatics and molecular modeling through simulation and free energy calculations using our Gromacs software. Specifically, we will work on:

MEMBRANE PROTEIN 3D MODELING
We will develop new methods for fold recognition, modeling, and refinement of membrane proteins based on predicted topology, fragment databases, and new implicit membrane models. This will subsequently be used for large-scale modeling of channels and receptors.

SIMULATIONS OF ION CHANNELS
The S4 helix of voltage-gated ion channels is exceptional due to its high charge. We will simulate how S4 is stabilized both in channels and model voltage-sensor domains to understand activation. With our latest Gromacs version we will also pursue 10-microsecond simulations of gating.

MODELING & DESIGN OF HELIX INTERACTIONS
Helix interactions are critical in large proteins, and we will develop methods to predict these by using marginally stable helices as a testbed. For isolated dimers we will investigate mutations by classifying sequences, work on better 3D models and predict dimerization energy to later attempt design of competing peptides
.

LIGAND DESIGN FREE ENERGY CALCULATION
We will develop free energy methods both for rapid approximations and more accurate simulations using Bennett Acceptance Ratios to screen and optimize predicted hits for a wide range of membrane transporters and channels.

Last updated on 2017-24-03 at 12:41