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Renko de Vries: Protein Polymers: simple designed proteins as models for complex biological assembly

Wanneer:do 15-02-2018 13:00 - 14:00
Waar:5115.0013

The de-novo design of proteins that assemble into well-defined nanostructures is now a rapidly developing field with many potential implications for both fundamental science and for applications. The sequences of many proteins that make up natural protein materials such as silks, elastin and collagen contain (imperfect) repeats of simple characteristic sequence motifs. We design sequences for new self-assembling proteins by combining (repeats) of such motifs in novel ways. As I will show, this "protein-polymer" approach is a very powerful way of designing new proteins with simple sequences but which nevertheless can have subtle self-assembly behavior, mimicking the self-assembly behavior of the much more complex natural proteins. As a first example I will discuss a minimalistic sequence for an artificial virus capsid protein. This very simple protein, with a design inspired by thermodynamic models for the assembly of the Tobacco Mosaic Virus, when mixed with DNA, spontaneously forms rod-shaped nanoparticles that each encapsulate a single DNA molecule. The assembly quantitatively follows the thermodynamic model that inspired its design. As a second example I will discuss the hierarchical assembly of artificial collagens into well-organized fibrils. As a first stage towards designing artificial collagens that assemble into well-defined fibrils in the same way as mammalian collagen-I, I have developed coarse-grained models and simulations that can be used to predict which interaction patterns (and hence which sequences) are required for the formation of well-defined fibrils of patterned semi-flexible rods.