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Rob Phillips
More books by Rob Phillips…
“In his paper entitled 'Bacterial Growth: Constant obsession with dN/dt,' Frederick Neidhardt (1999) tells us: 'One of life's inevitable disappointments - one felt often by scientists and artists, but not only by them - comes form expecting others to share the particularities of one's own sense of awe and wonder. This truth came home to me recently when I picked up Michael Guillen's fine book Five Equations That Changed the World and discovered that my equation - the one that shaped my scientific career - was not considered one of the five.”
― The Molecular Switch: Signaling and Allostery
― The Molecular Switch: Signaling and Allostery
“A general challenge for the models we have written here, but for theory more generally in biology, is to be ahead of the experiments. Ultimately, we want to suggest exciting and revealing experiments that have not yet been conceived or undertaken. One of the critical frontiers in this area is to design experiments that showcase the uniquely nonequilibrium features of living systems, providing an impetus for new kinds of statistical physics.”
― The Molecular Switch: Signaling and Allostery
― The Molecular Switch: Signaling and Allostery
“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.”
― The Molecular Switch: Signaling and Allostery
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.”
― The Molecular Switch: Signaling and Allostery
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