Synthetic nanomaterials from standardized protein blocks

In March, 2024, Huddy et al. in the team of David Baker (subsequently a Nobel Laureate) published a wide range of synthetic protein nanostructures self-assembled from standardized, engineered alpha-helical protein "building blocks"^[1]. The extensively documented report, in Nature, has 32 authors^[1].

The breakthrough here is that instead of designing a single "one-off" desired nanostructure, the Baker group has first designed a series of regular building blocks that can be assembled into diverse nanostructures using straightforward geometric principles. These now enable "construction of protein nanomaterials according to ‘back of an envelope’ architectural blueprints"^[1]. There are many potential applications, such as drug delivery or catalysis, which remain to be explored.

Building Blocks

In this project, the simplest building blocks consist of anti-parallel alpha helices engineered to be straight and flat, that is twistless helix repeat (THR) protein blocks. A simple example, THR1, is 8g9j, consisting of . Each helix is amphipathic, that is, hydrophobic on the side contacting other helixes, and hydrophilic on the side facing outwards (not shown). The , making a highly water soluble building block.

Related Work

Related work from the Baker group includes Bond-centric modular design of protein assemblies by Wang et al., 2024^[2].