Statistical mechanics studies of biological systems

The first study is based on the efforts by Y. Hamuro and W. F. DeGrado to synthesize antibiotic biomimetics based on beta-peptide structures (1). We performed molecular dynamics simulations of the interaction between the synthesized beta-peptides and membrane mimicking DPC micelles. The simulations helped our experimental collaborators to gain new insights into these interactions and to improve their agents.

The other projects were motivated by theoretical investigations of the energy transduction in the F1F0 ATP synthase by H. Wang and G. Oster (2). Two major questions are associated with the mechanism of its F1 subunit: First, the mechanism of ATP (un)binding to (and from) F1 and second, the reaction mechanism of ATP synthesis.

We investigated the (un)binding mechanism of ATP by performing a series of coupled molecular dynamics simulations, in which the structural changes in the binding site were driven by the interpolated coordinates of the binding unit's outer regions. In addition, we extended the transition path sampling method (3), which allows the characterization of an ensemble of transition states, to the characterization of intermediate states. This was motivated by previous studies of the reaction mechanism of ATP hydrolysis/synthesis, which showed that the reaction proceeds through unknown intermediates.

1. Y. Hamuro, J. P. Schneider, and W. F. DeGrado, J. Am. Chem. Soc. 121,
12200 (1999).

2. H. Wang and G. Oster, Nature 396, 279 (1998).

3. P. G. Bolhuis, C. Dellago, P. L. Geissler, and D. Chandler,
J. Phys. Condens. Matter 12, A147 (2000).