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) Interface-resolved network of protein-protein interactions. PLoS Comput Biol 9:e1003065
Grigoriu, Simina; Bond, Rachel; Cossio, Pilar et al. (2013) The molecular mechanism of substrate engagement and immunosuppressant inhibition of calcineurin. PLoS Biol 11:e1001492
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
Johnson, Margaret E; Hummer, Gerhard (2013) Evolutionary pressure on the topology of protein interface interaction networks. J Phys Chem B 117:13098-106
Johnson, Margaret E; Hummer, Gerhard (2012) Characterization of a dynamic string method for the construction of transition pathways in molecular reactions. J Phys Chem B 116:8573-83
Boura, Evzen; Ró?ycki, Bartosz; Chung, Hoi Sung et al. (2012) Solution structure of the ESCRT-I and -II supercomplex: implications for membrane budding and scission. Structure 20:874-86
Roýýycki, Bartosz; Boura, Evzen; Hurley, James H et al. (2012) Membrane-elasticity model of Coatless vesicle budding induced by ESCRT complexes. PLoS Comput Biol 8:e1002736
Wikstrom, Marten; Hummer, Gerhard (2012) Stoichiometry of proton translocation by respiratory complex I and its mechanistic implications. Proc Natl Acad Sci U S A 109:4431-6
Waghe, Aparna; Rasaiah, Jayendran C; Hummer, Gerhard (2012) Entropy of single-file water in (6,6) carbon nanotubes. J Chem Phys 137:044709
Zhu, Fangqiang; Hummer, Gerhard (2012) Theory and simulation of ion conduction in the pentameric GLIC channel. J Chem Theory Comput 8:3759-3768

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