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“A puzzle that remains in the field of allostery in this high-throughput era is that we have had very limited tools that allow us to answer the general question of which proteins in the proteome are allosteric and who their binding partners are. Despite Monod's characterization of the allostery phenomenon as the second secret of life, because of this important knowledge gap, as a field we are often flying blind because of our ignorance of how the key molecular players in the signaling pathways have their activity modified by other chemical agents, and because of our ignorance of the identity of those chemical agents themselves.

To that end, the emergence of mass spectrometry has provided an exciting opportunity to query not only the posttranslational modifications suffered by a given signaling molecule but also, because of recent innovations, when signaling molecules have bound a given small molecule. We see that by lysing cells in the absence and in the presence of some small-molecule allosteric effector candidate, some proteins will bind that small molecule and, as a result, be resistant to limited proteolysis by proteinase K. This means that when the proteins are denatured and trypsin digested, the pattern of cuts in the polypeptide chain will be different for any protein that was bound to the candidate small molecule. Approaches such as this hold the promise of systematic identification of the allosterome for any organism and will be a critical part of our resolution of the puzzles of how the macromolecules of the cell are controlled by a battery of small molecules.”
― Rob Phillips, The Molecular Switch: Signaling and Allostery

“The MWC equilibrium framework not only has been exploited for thinking about the activity of the chemotaxis receptors but also has served as a null model for the switching behavior of the bacterial flagellar motor. This motor switches between clockwise and counterclockwise rotation, as a result of the binding of CheY-P to the FliM part of the motor. The distribution of duration times in the counterclockwise rotation state of the motor appears to defy description in terms of the MWC model and Ising-type conformational spread model, instead demanding that the system operate out of equilibrium with constant energy dissipation. The emergence of such nonequilibrium effects where the MWC framework breaks down represents one of the most exciting frontiers for thinking about the function of allosteric molecules in the context of living cells.”
― Rob Phillips, The Molecular Switch: Signaling and Allostery