Competing interactions create functionality through frustration
- Department of Chemistry, University of Houston, Houston, TX 77204-5003
Like Buridan's Ass—and somewhat ironically—we often feel frustrated if given more choice than expected. Yet, the converse appears to be true as well. Frustration that results from the impossibility of satisfying all competing interests simultaneously itself implies a greater diversity of distinct behaviors for the overall system. Nature seems to use just this unsettling device of built-in conflict to ensure adaptability and functionality at many levels of organization, ranging from the molecular scale, as in protein-conformational dynamics, to the macroscopic scale, as in socioeconomic processes. Identification and quantitative characterization of the precise sources of frustration is key to understanding the workings of existing systems and the ability to design new, useful systems. This task, however, is difficult for two reasons: (i) direct computational studies of systems with many states are almost always costly and often are simply out of reach for today's computer technology, and (ii) once the calculation is done, even bookkeeping and grouping states are usually unobvious, again because the states are so many. In this issue of PNAS, Materese et al. (1) accomplish both tasks for the native state dynamics of a small protein, eglin c, which inhibits serine protease. By identifying the key conflicts between different physical interactions, they move us toward the goal of designing proteins that are not just sculptures but can also function.
Illustration of the analogy between the free-energy landscapes for liquid and protein-conformational dynamics. (A) The log-number of states (i.e., entropy), as a function of energy, for two systems with similar free-energy landscapes. At liquid-to-crystal transition, the system increases its entropy by phase separation and follows the red line, while bypassing the structural states intermediate between the liquid and crystal states. Analogously, to fold, the protein must bypass glassy, trap states that are intermediate between the numerous, highly mobile molten globule …
*E-mail: vas{at}uh.edu
