Self-Assembly of Helical Peptides (HelAssembly)
- Kód projektu
- Období řešení
- 1/2014 - 3/2014
- Investor / Programový rámec / typ projektu
- Masarykova univerzita
- Fakulta / Pracoviště MU
- Centrální řídící struktura projektu CEITEC
While nature readily forms peptide/protein-based materials with exceptional properties, we are still unable to artificially design similar hierarchical structures. Currently there is a lack of molecular understanding at different levels of self-assembly and the number of possible protein sequences to test is unmanageably large. Thus, at the moment, the development of new peptide-based materials is limited to assemblies observed in nature under in vivo conditions. In order to advance the state-of-the-art we propose to establish the principles of complex self-assembly of helical proteins from simple building blocks to large-scale aggregates and identify new structures. This will lay the foundation for the rational design and construction of hierarchical biomaterials with special properties such as adaptability, self-healing, or unusual strength, toughness etc.
To reach the proposed objective we will employ unique combination of multi-scale computer simulations complemented with the experimental confirmation of in silico predicted structures. Using computer simulations, which are an efficient tool to sample the available parameter space, we will determine sequences and conditions that lead to self-assembly of structures with various morphologies. To make the task feasible we propose to focus on proteins with a helical core, where we can exploit the 'knob-in-hole' mechanism of simple coiled-coils (coiled α-helices). We will develop a novel model for peptides that is able to capture sequence specificity of the mechanism but is also applicable to large-scale simulations at the same time. Furthermore, we will investigate the impact of the assembled structures on the permeability of phospholipid membrane in order to identify the cellular toxicity and their potential for use as channels or therapeutics. The insights gained will also contribute to the understanding of protein crystallization and protein folding, which is still a challenge after 50 years.