POSTERS - BLAST X - University of Utah

BLAST X Poster #62
MODELLING MCP SIGNALLING MECHANISMS WITH HIGH-THROUGHPUT SIMULATION
OF Tar TM2
Benjamin A Hall, Mark SP Sansom
Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU
Transmembrane helices play a multiple vital roles in cell function, including intercell
signalling processes, channel gating and active transport. As such, there exists a considerable
amount of data on the biological function and structural properties of naturally occurring helices
and their mutants. Simulation studies can provide insight into the dynamics and behaviour of
biomolecular systems in a variety of environments, but however such analyses are
computationally expensive and typically difficult to automate. Coarse grain simulations are
becoming an increasingly popular tool for understanding the properties of biological systems,
overcoming canonical limits of atomistic simulations such as timescale or system size. Both
such techniques involve several manual steps, including system build, simulation set up and
analysis. Here we present Sidekick, a piece of software which automates these processes to
allow for the set up of massive numbers of coarse grain simulations on the basis of a small set
of input sequences, or a single sequence and a scanning mutation. We demonstrate the use of
this software to approach the mechanism of signalling in the MCPs, based on existing
mutational data for TM2 from different MCPs and organisms. By observing the change in
positions and orientations of the helix with different mutations, we propose that a piston model
dominates the signalling event, though there may be a lesser role for rotation of the helix.
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