Speaker
Igor Drobnak
(National Institute of Chemistry, Slovenia)
Description
The design of novel proteins to efficiently carry out specific tasks is one of the major long-term goals in biomolecular research. This task is made extremely difficult by the large number of degrees of freedom in protein structures and by the large number of competing interactions that contribute to protein stability. Recent work by our group has demonstrated that the problem can be made more tractable by arranging modular, specifically interacting elements into a sequence that ensures only a specific folded structure will satisfy all available pairwise interactions [1,2]. This concept of topological protein design was used to produce a tetrahedral protein composed of orthogonal coiled coil segments [2]. We have now set out to investigate and optimize its folding pathway - the order in which the individual coiled coil modules form their specific pairwise interactions. Some pathways may allow for smooth folding while others could introduce unnecessary free energy barriers that slow down folding and increase the probability of misfolding and aggregation. We are using Gō model molecular dynamics to determine the preferred order in which native coiled coil pairs are most likely to form. These predictions are combined with experimental data to determine how different arrangements of the same building blocks affect the kinetics of folding. With this knowledge we will be able to design an optimized version of the tetrahedron, whose folding pathway will be as smooth and free of energy barriers as possible.
1. Kočar et al. (2014), *WIREs Nanomed. Nanobiotechnol.* **7**:218.
2. Gradišar et al. (2013), *Nat. Chem. Biol.* **9**:362.
Primary author
Igor Drobnak
(National Institute of Chemistry, Slovenia)
Co-authors
Dr
Ajasja Ljubetič
(National Institute of Chemistry)
Dr
Helena Gradišar
(National Institute of Chemistry, Slovenia)
Karen Butina
(National Institute of Chemistry, Slovenia)
Prof.
Roman Jerala
(National Institute of Chemistry)
