Protein design: flexible components allow new architectures

Enlarge

Artificially designed proteins are usually based on building blocks that obey strict rules of symmetry. As such, their structure can generally be predicted using computer simulations. But there are exceptions: Some proteins designed on computers exhibit surprising new structures or properties that could be useful. An international team led by Professor Alena Khmelinskaia from the Department of Chemistry at LMU and Professor Neil King from the University of Washington has now discovered why this is the case: Some proteins contain flexible components and can take on more than one structure. These findings could open up new avenues for the development of customized proteins.

In their study, the researchers analyzed three designer proteins which exhibited significantly different structures in experiments than predicted. These proteins are synthetized as follows: First, two or three of the starting materials react with each other and form so-called dimers or trimers. By means of self-assembly, these dimers and trimers are then supposed to produce highly symmetrical structures such as icosahedra or octahedra. However, this did not always occur: In addition to the pre-calculated structures, the researchers also found quite a number of particles that were substantially larger or had even formed completely different architectures.

Full press release

A. Khmelinskaia et al.: Local structural flexibility drives oligomorphism in computationally designed protein assemblies. Nature Structural & Molecular Biology 2025