Member Listing – Florian Praetorius

Biomolecular design with proteins and/or nucleic acids

In biology, structure and function are deeply interconnected. Proteins fold into intricate three-dimensional shapes that define their functions, and multiple proteins are often arranged in large molecular assemblies with functions that arise from their global shape or from the relative arrangement of their building blocks. Molecular design allows us to create new shapes and structures with novel or optimized functions. The Praetorius lab specializes in two types of biomolecular building blocks: proteins and nucleic acids. We use deep learning-based computational design tools like hallucination, diffusion, and ProteinMPNN as well as more conventional physics-based protein design tools like Rosetta to generate new proteins from scratch. On the experimental side we use biochemical and biophysical methods to characterize these de novo designed proteins in the lab. To reach length scales that are currently not accessible to protein design we use nucleic acid nanotechnology, in particular DNA Origami. Ultimately, we aim to combine the two design approaches, protein design and DNA nanotechnology, to generate novel types of DNA-protein hybrid assemblies with functions and properties that would not be accessible to either technique alone. Our goal is to develop a general platform for controlling the spatial arrangement of functional protein domains with molecular precision on the nanometer- to micrometer scale in molecular assemblies that can respond to external stimuli, allowing triggered rearrangement or dissociation. We plan to use this platform to study the complex connection between structure and function, for example in the context of receptor-ligand interactions, and to create novel tools for applications as diverse as biosensing, gene delivery, gene editing, or vaccine development.

protein design

2018