Protein Sociology: Collective Interaction Behaviors

SH2 domain structureAs always, it’s these odd conjunctions of things that don’t go together that catches the eye. In this case, molecular and sociology. The actual article1 is much more mundane and true to the correct science jargon, and included in a special section of the most recent Nature on “Proteins to Proteomes.” It’s also a nice article that examines a broad array of topics in molecular biology.

Of greater interest and with a slightly less catchy title, is another article on the section: Reaching for high-hanging fruit in drug discovery at protein–protein interfaces2. The abstract:

Targeting the interfaces between proteins has huge therapeutic potential, but discovering small-molecule drugs that disrupt protein–protein interactions is an enormous challenge. Several recent success stories, however, indicate that protein–protein interfaces might be more tractable than has been thought. These studies discovered small molecules that bind with drug-like potencies to ‘hotspots’ on the contact surfaces involved in protein–protein interactions. Remarkably, these small molecules bind deeper within the contact surface of the target protein, and bind with much higher efficiencies, than do the contact atoms of the natural protein partner. Some of these small molecules are now making their way through clinical trials, so this high-hanging fruit might not be far out of reach.

Just two good, general reviews for the aspiring molecular biologist.

  1. Robinson CV, Sali A, Baumeister W. The molecular sociology of the cell. Nature 450:973-982 (2007) DOI:10.1038/nature06523
  2. Wells JA, McClendon CL. Reaching for high-hanging fruit in drug discovery at protein–protein interfaces. Nature 450:1001-1009 (2007) DOI:10.1038/nature06526

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