Speaker
Description
Proteins are machines, and machines are defined by what they do, not just what they look like. Yet almost everything we know about protein structure comes from snapshots: frozen moments from crystallography or cryo-EM, and now predicted scaffolds from AlphaFold. To understand how an enzyme interacts with a substrate, how a drug binds its target, or how a transporter pumps an ion, we need to watch and not just look.
Time-resolved serial crystallography turns crystallography into film. Using X-ray free-electron lasers and the new generation of synchrotrons, we can now follow proteins in action on timescales from femtoseconds to seconds. I will introduce how these experiments work, without assuming a crystallography background, and show what they have revealed - including the femtosecond-to-millisecond trajectory of a photoactivatable cancer drug being released from its target.
The technique is not yet routine. I will describe how my group is tackling its main bottlenecks through new data acquisition, analysis, and refinement strategies, and how we are applying these tools to RuBisCO, the enzyme that catalyzes biological carbon fixation and whose mechanism has remained elusive for forty years.