An essential characteristic of our work is that the hypotheses and interpretations we provide be supported by direct experimental evidence. Indeed, through a close and ongoing collaboration with the Rudnick group at Yale University, we have very recently obtained new insights into the neurotransmitter:sodium symporters (see second figure for a homology model of serotonin transporter, SERT) in two important areas: first, regarding the mechanism by which they couple to chloride ions; and second, the formation of alternate conformations. Similar methodologies were used for developing models of glutamate transport, in collaboration with the Kanner group at Hebrew University, Jerusalem. We are also keen to collaborate with other experimentalists here in the MPI, in part supported by the collaborative research grant, SFB807. For example, with Christine Ziegler, we are combining computational, structural and biochemical studies on the betaine glycine transporter, BetP, which is providing key insights on the mechanisms of transport and regulation.

We apply a range of computational tools to attempt to understand these processes at atomic detail. To date, specific techniques include sequence analysis and continuum electrostatics, as well as protein structure prediction and molecular dynamics simulation. This work builds on previous studies carried out in the Honig and Woolf labs, in which we identified effective methods for predicting the structures of membrane proteins.