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    Scientists Investigate Randomness in Protein Interactions

    Proteins perform distinct and well-defined tasks, but little is known abouthow interactions among them are structured at the cellular level. Now, two physicistsreveal that ‘#151; at least in yeast cells ‘#151; these interactions are notrandom, but well-organized.

    ‘Although scientists understand how a given protein interacts with otherproteins, the way they connect with each other as a whole remains mysterious,’said Sergei Maslov, a physicist at the U.S. Department of Energy’#146;s BrookhavenNational Laboratory (BNL), one of the study’#146;s two authors.

    For the last 10 years, Maslov, an expert in statistical physics, has been studyingcomplex systems such as collections of particles, proteins and networked computers.In the new study, Maslov and physicist Kim Sneppen of the Norwegian Universityof Science and Technology used computer modeling to look at how proteins interactwith each other.

    Although scientists know that some proteins are very busy ‘talking’to many other proteins, Maslov and Sneppen discovered that such highly connectedproteins are unlikely to ‘talk’ to each other.

    The scientists think that proteins interact this way to reduce interferenceamong the messages of proteins that crisscross each other in the cell.

    The other possible advantage of this protein interaction pattern is to makethe protein network inside the cell more stable.

    ‘Proteins with many connections seem not to want to be disturbed by wrongmessages or anything ‘#145;harmful’#146; to these proteins,’ Maslov said.

    To determine which among the 6,000 yeast proteins interact with each other,Maslov and Sneppen collected data on protein interactions in yeast cells froma public database. They then compared the resulting network of interactionsto a simulated pattern ‘#151; produced by a computer-modeling program ‘#151;in which proteins interact randomly.

    ‘If you took a given number of proteins and distributed interactions amongthem randomly, you would hardly find any particular protein that would havea lot of interactions. Proteins would all ‘#145;talk’#146; randomly with eachother in such a network,’ Maslov said. ‘So, hubs of highly-interactingproteins are not something that you would expect to happen by pure chance.’

    The researchers did, however, observe hubs of interacting proteins in the yeastcells. The connections between hub proteins reveal an ’emergent property’that acts beyond the level of the functions of the individual proteins and makesthem act together to coordinate their functions. Studying these interactionscan help identify these coordinated functions, and may also reveal intrinsicfeatures of the interacting proteins.

    The ‘holistic’ approach taken by Maslov is part of an ongoing interdisciplinaryeffort in which scientists are trying to understand phenomena involving manyproteins, such as diseases. The understanding of how protein interaction networksare designed might, for instance, help scientists better understand the causesof cancer. One of the hubs in the human protein network, called p53, has a majorrole in preventing cells from developing into a tumor.

    ‘The computer modeling program developed in this work can be applied tointeractions in other networks such as food webs in ecosystems, neural networks,the Internet, and even among stock market agents,’ Maslov said.

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