Celebrating the 2024 Nobel Prize in Chemistry

We’re big fans of all our depositors here at Addgene — your contributions make the repository what it is. So we’re thrilled this week to congratulate depositor David Baker, who was awarded the Nobel Prize in Chemistry last week alongside Demis Hassabis and John Jumper! The Baker Lab focuses on designing entirely new proteins, improving our understanding of how protein folding works and creating biological tools not found in nature.

Dr. Baker’s team was the first to develop and publish a human-designed protein that was not based on any existing protein structures, called Top7.

Figure 1: Top7 receives the Nobel Prize. Created with BioRender.com.

Top7 gets its name from “topology of protein” diagrams, which show the interactions between amino acids in an approximate, two-dimensional map. The Baker Lab wanted to create a new fold that is not present in nature (at least that we’ve seen so far!). They started by designing a novel topology, then iteratively generated 3D models and amino acid sequences that got closer and closer to achieving it.

Once they designed the protein computationally, the researchers expressed, purified, and characterized it, producing crystal structures demonstrating “the structure is strikingly similar to the design model at atomic resolution” (Kuhlman and Dantas et al., 2003). That made it a powerful proof of concept that this kind of protein design is possible.

Although Top7 was designed simply to be stable and novel, the principles that created it have been applied to numerous other protein design goals, both from the Baker Lab and others. The introduction of de novo designed proteins also helped researchers understand more about the biophysics of protein folding and selective pressures during protein evolution.

The Baker Lab has deposited multiple Top7 plasmids at Addgene, along with other tools like high resolution Ras sensors and crosslinked peptides proposed as a scaffold for a new generation of drugs, all developed with their protein design approach.

Congratulations to David Baker, Demis Hassabis, and John Jumper!

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References

Kuhlman, B., Dantas, G., Ireton, G. C., Varani, G., Stoddard, B. L., & Baker, D. (2003). Design of a Novel Globular Protein Fold with Atomic-Level Accuracy. Science, 302(5649), 1364–1368. https://doi.org/10.1126/science.1089427