We have made significant progress in several areas related to protein dynamics, folding, binding, and function. By combining atomistic simulations and experiments, we are able to determine a first structure of calcineurin bound to a substrate. This work was carried out in collaboration with the groups of Profs. Peti and Page (Brown University) and Prof. Martha Cyert (Stanford). The structure provides us with a better understanding of the mechanisms used to regulate this important signalling protein, and of the molecular mechanisms involved in immunosuppression. We also gained new insight into the function of the ESCRT machinery. ESCRT proteins are a major player in membrane protein trafficking and other cellular processes, and are hijacked by viruses, in particular HIV. By using a an elastic membrane model we could determine an energetically and kinetically viable mechanism of ESCRT-induced vesicle formation as a key step in ESCRT function. In collaboration with the group of Dr. Anfinrud at the NIH, we could also determine early intermediate structures and the structural dynamics of the photoactivated protein PYP. This work combined time-resolved x-ray crystallography with quantum chemical calculations. We also made significant progress in the characterization of protein-protein interaction networks. We introduced the interface interactions network to establish a more detailed and structurally informative view of the interaction network. On this basis, we could provide evidence for evolutionary pressure acting on the topology of the interaction network to suppress competition from non-specific interactions.

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Johnson, Margaret E; Hummer, Gerhard (2013) Evolutionary pressure on the topology of protein interface interaction networks. J Phys Chem B 117:13098-106
Kofinger, Jurgen; Hummer, Gerhard (2013) Atomic-resolution structural information from scattering experiments on macromolecules in solution. Phys Rev E Stat Nonlin Soft Matter Phys 87:052712
Best, Robert B; Hummer, Gerhard (2009) Optimized molecular dynamics force fields applied to the helix-coil transition of polypeptides. J Phys Chem B 113:9004-15
Ren, Xuefeng; Kloer, Daniel P; Kim, Young C et al. (2009) Hybrid structural model of the complete human ESCRT-0 complex. Structure 17:406-16
Turjanski, Adrian Gustavo; Hummer, Gerhard; Gutkind, J Silvio (2009) How mitogen-activated protein kinases recognize and phosphorylate their targets: A QM/MM study. J Am Chem Soc 131:6141-8