Presidential Lectures are a series of free public colloquia spotlighting groundbreaking research across four themes: neuroscience and autism science, physics, biology, and mathematics and computer science. These curated, high-level scientific talks feature leading scientists and mathematicians and are designed to foster discussion and drive discovery within the New York City research community. We invite those interested in these topics to join us for this weekly lecture series.
One of the characteristic features of life is specificity. It emerges in metabolism, information transfer from DNA to protein, embryology, immunology and virtually every other process. Its explanation on the molecular level is thermodynamic stability and structural complementarity. Yet one disturbing issue persists: the protein and nucleic acid sequences coding for that specificity are generally too small to distinguish actual partners from competitors. Similarly, protein degradation conveys specificity through very short sequences. The process is so kinetically complex that bulk kinetic experiments and a few molecular structures are insufficient to explain how specificity is achieved. Using single molecule kinetic measurements, we have deconvolved much of that specificity. The results reveal a novel process based loosely on some original ideas of kinetic proofreading, by John Hopfield and Jacques Ninio. The unraveling of the details of the ubiquitin mechanism has led us to think more generally about the tradeoffs in biology between specificity and speed and the limits to which energy consumption can optimize that tradeoff. These conclusions based on understanding the mechanism of protein degradation may be relevant to other biochemical processes, such as phosphorylation and transcription.