Forces and Conformational Dynamics in Biomolecular Nanomachines

Thursday, 28. Februay, 8:30 h, H 0105

Many proteins are molecular ’nano machines’; their conformational plasticity and dynamics determines their function. Molecular dynamics force probe experiments enable one to simulate and predict such conformational motions at the atomic level and permit comparison with single molecule experiments [1-4].

Three examples shall highlight the role of conformational protein motions and their theoretical description [7,8]:

Aquaporins are highly selective water channels. Molecular dynamics simulations of multiple water permeation events correctly predict the measured rate and explain why these membrane channels are so efficient, while blocking other small molecules, ions, and even protons [5].
Primary ATP synthesis steps in F1-ATP synthase were studied with molecular dynamics simulations. By enforced rotation of the gamma-‘stalk’, as in vivo caused by protonmotive Fo-rotation, a timeresolved atomic model for the mechano-chemical energy transfer to the ATP synthesis sites is obtained [6].
Importins and exportins bind cargo proteins and facilitate their transport across nuclear pores. Our molecular dynamics simulations predict the unbound highly flexible importin structures, explain the exportin ’loaded spring’ dynamics, and thus resolve previous energetic and kinetic puzzles. [4]

[1] H. Grubmüller, B. Heymann, P. Tavan (1996) Science 271, 997-999
[2] L.V. Schäfer and E.M. Müller and H.E. Gaub and H. Grubmüller (2007) Angewandte Chem. Intl. Ed. 46, 2232-2237
[3] F. Gräter, H. Grubmüller (2007) J. Struct. Biol. 157, 557-569
[4] U. Zachariae, H. Grubmüller (2006) Structure 14,1469-1478
[5] B.L. de Groot, H. Grubmüller, Science 2001, 294, 2353-2357
[6] R. Böckmann, H. Grubmüller, Nature Struct. Biol.. 2002, 9, 198-202
[7] F. Gräter, J. Shen, H. Jiang, M. Gautel, H. Grubmüller (2005) Biophys. J. 88,790-804
[8] J.J. Sieber et al. (2007) Science 317, 1072-1076

Helmut Grubmüller
Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen