A New Generation of Idealized Protein Building Blocks Enables Rational Nanomaterial Design

Abstract

Humans build complex structures by utilizing intuitive building blocks. Bricks, wooden planks, plumbing fittings, and most other building materials all have features that help humans to use them and share ideas of how to work with them. In contrast, the design of novel protein nanomaterials has been difficult due to the irregular shapes and behaviors of naturally-evolved proteins. Even when new protein complexes can be modeled, it remains a challenge to assign sequences to the models for them to form correctly when expressed. In this work, we have made a new generation of protein building blocks with features that are amenable for building in the protein world. The blocks are designed helical repeat (DHR) proteins with explicitly-defined brick-like geometry. They are built from alpha helices that are straight (not supercoiled at all) and have their helical axes all parallel to each other. This strict specification allows us to model protein assemblies with simple blueprint representations. With this new building block set, we have been able to design and characterize new protein assemblies with unprecedented modularity.