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Our research program is centered on the interplay between structure and function in protein evolution. Currently, two main foci are prevalent in our research; protein structure evolution and protein pathway evolution.
Are protein domains with similar structure, no statistically significant sequence identity, and diverse functions remote homologs?
For this project we are focusing of the superfold domains. Our methodology for this project involves a journey back in time. First, structurally similar domains are identified and for a non-redundant set, protein families are built. For the root of each family, the ancestral sequence is reconstructed and modeled using homology modeling. Then we test whether the root models are closer to each other than the actual structures, using a structure-sequence distance method.
How do disordered proteins evolve? Can they drive neostructuralization?
The structurally disordered proteins have high conformational flexibility and often promiscuous activity. Here, our primary interest is to investigate how the disordered regions in a protein evolve after a gene duplication event. As gene duplications result in functional redundancy, the retention of two or more copies implies that there may be sub- and/or neofunctionalization occurring with the duplicated protein family. The different copies are likely to experience different functional and structural constrains. For proteins that originally had high conformational and functional flexibility, it seems plausible that the conformational and functional ensembles may evolve in different directions for different copies. We are hence combining a phylogenetic approach with structure prediction methods to investigate how disorder and secondary structure propensities vary over time. In parallel we are also investigating how phosphorylation change over time in the disordered proteins, since phosphorylation is an important regulator of structure and function for the disordered regions.
Protein pathway evolution
Within the project of protein pathway evolution, we are currently studying the dopamine and serotonin pathways. As these two parallel pathways share one enzyme and use another duplicated enzyme family extensively, they seem to have co-evolved. We are analyzing how the different families within these pathways have evolved, with regard to phylogenies, gene duplications and functional change.